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Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128
Open accessAbstract
MicroRNAs, the non-coding single-stranded RNA of 19-25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases.
Overview
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TL;DR
This review summarizes brain microRNAs, with a focus on brain-enriched miRNA-128 in neuronal differentiation, brain tumors, apoptosis, angiogenesis, and cholesterol metabolism. It compiles validated targets and bioinformatic analyses suggesting conserved miRNA-128 targets and enriched signaling pathways relevant to cancer and metabolic disease.
Key findings
- The brain expresses more distinct miRNAs than any other vertebrate tissue; 70% of known miRNAs are expressed in the brain, though only a handful are brain-specific or brain-enriched. Sempere et al. identified 17 miRNAs expressed in mouse and human brain, including miR-128.
- miRNA-128 is transcribed by two genes: miRNA-128-1 in R3HDM1 on chromosome 2q21.3 and miRNA-128-2 in ARPP21 on chromosome 3p22.3. It is induced during neuronal differentiation and is downregulated in glioblastoma, medulloblastoma, and neuroblastoma, and deregulated in autism, prion-induced neurodegeneration, Huntington disease, Parkinson disease, and Alzheimer disease.
- Validated miRNA-128 targets/effects include Bmi-1, E2F3a, EGFR, PDGFRα, Reelin, DCX, SNAP25, SIRT1, Bax, and ABCA1/ABCG1/RXRα. Depending on cell type, miRNA-128 can be pro-apoptotic or anti-apoptotic, and it regulates proliferation, self-renewal, invasion, angiogenesis, and cholesterol homeostasis.
- Bioinformatic analysis identified 90 miRNA-128 targets conserved among 9 species. PANTHER and GeneCodis enrichment showed insulin/IGF-MAPK, TGF-beta, angiogenesis, PI3K, and Wnt pathways among the most enriched; insulin and chemokine signaling were enriched in both analyses (p < 0.05), and metabolic process was the highest-rated biological process by PANTHER.
Methods
- Literature review of brain microRNAs and miRNA-128, with tables summarizing brain-enriched and brain-specific miRNAs, their validated targets, functions, and disease associations.
- Bioinformatics: predicted miRNA-128 targets from TargetScan 5 for nine species (human, mouse, chimpanzee, rhesus, cow, chicken, frog, rat, opossum), filtered to 90 targets conserved across all nine species, then pathway enrichment using PANTHER and GeneCodis.
- No primary wet-lab experiments are reported in this review; it synthesizes prior studies, including the authors’ own published work.
Limitations
- The authors state that high-throughput target validation methods are lacking, many cellular functions and pathways affected by miRNA-128 remain undiscovered, and regulation of Wnt and chemokine signaling by miRNA-128 needs further validation.
- The authors state that their in vitro cholesterol results require in vivo validation, that the role of miRNA-128a in HIV-1 encephalopathy needs to be determined, and that it is not known whether miRNA-128 changes in cancer are a cause or effect of disease.
- Evident from the text: as a review, conclusions depend on cited studies; miRNA-128 shows context-dependent pro-apoptotic and anti-apoptotic roles and both up- and down-regulation across diseases, limiting simple therapeutic generalization.
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In the paper
“we also demonstrated that miRNA-128 augments the antitumor effects of compounds (Etoposide and Cisplatin).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
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“We provided the first evidence of miRNA-128-2 to be a new regulator of cholesterol homeostasis [277].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Insights into regulation of cholesterol metabolism by miRNA-128: a new key player in cholesterol related disorders
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“metabolic process came out to be the highest rated biological process with maximum number of genes during PANTHER Analysis (Figure 5).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Biological relevance of miRNA-128 as revealed by bioinformatic analysis
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“insilico analysis of transcription factor binding sites of these two genes reveals almost similar pattern of transcription factors (unpublised data).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Future directions/conclusions
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“over expression of miRNA-128 in HEK293T cells led to an increase in reactive oxygen species [57].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
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“miRNA-128 also regulates cholesterol metabolism and fatty acid biosynthesis pathways.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Insights into regulation of cholesterol metabolism by miRNA-128: a new key player in cholesterol related disorders
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“we discovered that 90 targets of miRNA-128 were conserved among 9 species (Human, Mouse, Chimpanzee, Rhesus, Cow, Chicken, Frog, Rat, Opossum)”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Biological relevance of miRNA-128 as revealed by bioinformatic analysis
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“we recently observed that miRNA-128 overexpression induced apoptosis by down regulation of Bax and up regulation of p53 and Bak [57].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
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“we observed that the Insulin signaling pathway and chemokine signaling pathway were the enriched categories (p-value < 0.05) in both PANTHER and GeneCodis analysis.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Biological relevance of miRNA-128 as revealed by bioinformatic analysis
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“Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, TGF-beta signaling pathway, Angiogenesis, Insulin/IGF pathway-protein kinase B signaling cascade, PI3 kinase pathway, Wnt signaling pathway were found to be the most enriched biological pathways as revealed by the PANTHER analysis (Figure 4).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Biological relevance of miRNA-128 as revealed by bioinformatic analysis
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“transcriptome analysis of miRNA-128 overexpressed cells revealed that miRNA-128 inhibits SIRT1 expression directly through a miRNA-128 binding site within the 3′UTR of SIRT1”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
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“miRNA-128 further affected cholesterol efflux pathway by direct targeting ABCA1, ABCG1 and RXRα (Figure 2).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Insights into regulation of cholesterol metabolism by miRNA-128: a new key player in cholesterol related disorders
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“Allelic loss in chromosome 3p, where miRNA-128-2 is present, has also been associated with the most aggressive forms of neuroblastoma [213].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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“They also observed that the decrease of miRNA-128 is coupled with significant increase in the expression of Bmi-1, the transcription factor E2F-3a and angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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- Not matchedcites [236]
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“They observed Tat mediated deregulation of miRNA-128, in primary cortical neurons during the infection of neurons by HIV-1.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“The brain expresses more distinct and largest number of miRNAs than any other tissue in vertebrates as it has wide variety of cell types, neuronal and nonneuronal (for e.g. astrocytes) [29].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction
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“Down regulation of miRNA-128 has been reported in several brain cancers for example- glioblastoma [213] and medulloblastoma [235].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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“Roth et al. recently reported upregulation of miRNA-128 in the blood samples of glioblastoma patients compared to healthy controls”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“miRNA-128-2 is in the ARPP21 (cyclic AMP-regulated phosphoprotein, 21 kDa) on chromosome 3p22.3 [57].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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“Surprisingly, only a handful of microRNAs are expressed in a brain specific or brain-enriched manner [51].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
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In the paper
“These data suggest that miRNA-128 may suppress cancer pathogenesis by inducing differentiation out of a stem cell-like state.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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“Increased expression of these factors may explain the undifferentiated, self-renewing state of brain cells and de-regulated cell-cycle signaling pathways that support cellular proliferation in glioma and GBM [236].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“miRNA-128 | Reelin, DCX, SUZ12, neurofibromin 1, BMI1, RTK, EGFR,PDGFRαUPF1, MLN51, NTRK3, WEE1, Bax, E2F3a, SNAP25”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
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In the paper
“MiRNA-128 is transcribed by two distinct genes, miRNA-128-1 and miRNA-128-2 in two primary transcripts, which are processed into an identical mature miRNA sequence.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“Besides these, levels of miRNA-128 have been reported to be deregulated in autism, prion-induced neurodegeneration, Huntington disease, Parkinson disease and Alzheimer disease [239-242].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“Eletto et al. in his study showed that miRNA-128a inhibits expression of the pre-synaptic protein SNAP25 by binding to its 3′UTR (Figure 2).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“hence miRNA-128 may be used against the “stem cell-like” characteristics of glioma cells [237].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“Cui et al. demonstrated that the down-regulation of miRNA-128 inversely correlates with tumor grade.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“Zhang et al. in his study showed that brain-enriched miRNA-128 was also down regulated in glioma tissues and cell-lines”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“Several evidences in the literature show that under different biological conditions, expression patterns of miRNA-128 varies i.e. in some instances, it is up regulated whereas in some, it is down regulated (Table 3).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
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In the paper
“Interestingly, miRNA-128 and miR-124 are not only down regulated in gliomas but also other brain cancers including medulloblastomas and neuroblastomas [212,214].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Dysfunction of microRNAs in brain tumors
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In the paper
“whereas miR-124 and miR-128 are unique for neurons”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
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In the paper
“Shi et al. observed that miRNA-128 overexpression inhibited tumorigenesis and angiogenesis through targeting p70S6K1 and suppressing downstream molecules of p70S6K1 such as HIF-1 and VEGF [273].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
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In the paper
“miRNA-128 was found to target Bax in breast cancer cell line MDA-MB-231”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
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In the paper
“ginsenoside Rh2, a triterpene saponin has also been found to inhibit glioma cell proliferation by upregulating microRNA-128 [263].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
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- Not matched
In the paper
“ectopic expression of miRNA-128 in human glioma neurosphere cultures (having stem-like properties) led to reduction in glioma neurosphere number and volume by down regulating Bmi-1 (Figure 2) [60].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [60]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“loss of heterozygosity (LOH) of MicroRNA-128b in tumor samples correlated significantly with clinical response and survival following Gefitinib via EGFR [249].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [249]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Data from several independent studies showed that overexpression of miRNA-128 inhibits cell motility and invasiveness.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Messi et al. described DCX as a marker of SK-N-SH neuroblastoma cells that show high motility and invasiveness [269].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [269]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Kotani et al. in his study reported down regulation of miRNA-128 in MLL-AF4 Acute Lymphocytic Leukemia”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [254]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [258]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“downregulation of miRNA-128 sensitised MDA-MB-231 cells to chemodrugs [265].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [265]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Over expression of Bmi-1 oncogene has been found to promote NSC self-renewal by repressing the p16Ink4a and p19Arf senescence pathways [274].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [274]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“With respect to miRNA-128, it is known that miRNA-128 may act as a tumor-suppressor.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [254]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [258]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Khan et al. revealed down regulation of miRNA-128 in invasive prostate cancer cells as compared to benign prostate epithelial cell lines, where its levels are elevated [254,258].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [254]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [258]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“strong induction of miRNA-128 has been observed in endometrial cancer [260]”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [260]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“further confirms the role of miRNA-128 in promoting cellular senescence.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“over expression of miRNA-128 leads to an alteration in the expression of genes implicated in cytoskeletal organization (via truncated isoform of NTRK3) as well as genes involved in apoptosis, cell survival and proliferation, including the anti-apoptotic factor BCL2 in SH-SY5Y neuroblastoma cells [63].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [63]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that these two genes may presumably resulted from a gene duplication event.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Future directions/conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on the above information, we can say that depending upon the cell type; miRNA-128 can have anti-apoptotic as well as pro-apoptotic functions.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“They have shown using qRT-PCR that miRNA-128 levels were reduced in invasive prostate cancer cells as compared to benign prostate epithelial cell lines.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [258]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“thereby indicating possible mechanistically conserved functions of this miRNA (Figure 3).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Biological relevance of miRNA-128 as revealed by bioinformatic analysis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Evangelisti et al. proved that overexpression of miRNA-128 reduces neuroblastoma cell motility and invasiveness by targeting Reelin and DCX (Figure 2) [55].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [55]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“As miRNA-128 directly targets Bmi-1 oncogene”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [62]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Their study identified a link between miRNA-128 and p70S6K1 axis, which plays a vital role in glioma angiogenesis (Figure 2).”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [273]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“MiRNA-128 found to regulate its direct target Bmi-1 and PTEN-AKT pathway in pituitary tumors [62].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [62]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“several independent studies have illustrated the anti-proliferative role of miRNA-128 in glioma cells and glioblastoma cell lines [58,236].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [236]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“and it enhances resistance to conventional anticancer therapies [262]”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [262]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
- It may state two separate claims as one. 18
- Probably not a substantial claim. 18
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miRNA-128 up-regulated cholesterol synthesis genes and down regulated fatty acid biosynthesis genes.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Insights into regulation of cholesterol metabolism by miRNA-128: a new key player in cholesterol related disorders
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“we found that miRNA-128 induces apoptosis in wild type (WT) p53 as well as in mutant p53-expressing cells in a p53-dependent and -independent manner via induction of PUMA in MCF7, MDA-MB-231, HCT116 p53 +/+ and HCT116 p53 -/- cells respectively [264].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [264]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Similar to miR-124, miRNA-128 is induced during brain development and in differentiating neuronal cells”
- Also stated in: § Abstract · plain
“In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
What the sources say
- Not matchedcites [56]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Abstract · plain
In the paper
“Godlewski et al., reported that overexpression of miRNA-128 reduces glioma cell proliferation by downregulating Bmi-1 (B lymphoma mouse Moloney leukemia virus insertion region 1), decrease in histone methylation (H3K27me3) and Akt phosphorylation and up-regulation of p21CIP1 levels [60].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
What the sources say
- Not matchedcites [60]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Papagiannakopoulos et al. recently showed that miRNA-128 represses growth and enhances neuronal differentiation of glioma-initiating neural stem cells (giNSCs) by downregulating oncogenic receptor tyrosine kinases (RTKs), epithelial growth factor receptor (EGFR) and platelet-derived growth factor receptor-α (PDGFRα) (Figure 2) [59].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
What the sources say
- Not matchedcites [59]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Literature reveals that a single miRNA can target several mRNAs together, and a single mRNA can be targeted by different miRNAs in a concerted manner.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction
What the sources say
- Not matchedcites [25]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“overexpression of miRNA-128 inhibited cellular proliferation through negatively regulating E2F3a, which is highly expressed in glioma and important for cell cycle progression (Figure 2) [58].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
What the sources say
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“leading to repressed NMD (Nonsense-mediated decay) and the consequent upregulation of batteries of mRNAs encoding proteins important for neuron differentiation and function [56].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
What the sources say
- Not matchedcites [56]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“MiRNA-128-1 is embedded in the R3HDM1 (R3H domain containing 1) gene on chromosome 2q21.3”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
What the sources say
- Not matchedcites [57]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“As Bmi-1 is also known to promote the stem cell renewal, a process that is important in glioma”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
What the sources say
- Not matchedcites [237]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Literature reveals that 70% of known miRNAs are expressed in the brain [50].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
What the sources say
- Not matchedcites [50]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“There are a few reports which have talked about the involvement of miRNA-128 in TGF-β signaling [282] and PI3 kinase pathway [60].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Biological relevance of miRNA-128 as revealed by bioinformatic analysis
What the sources say
- Not matchedcites [282]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [60]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Up regulation of miRNA-128 not only suppressed the colony formation ability and invasiveness of pituitary tumor cells but also suppressed pituitary GH3 tumor growth in xenografts via, Bmi-1.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [62]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“over expression of miRNA-128 attenuated invasion in prostate cancer cells while its knockdown induced invasion in benign prostate epithelial cells as revealed by matrigel invasion assay [258].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [258]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“as well as in acute lymphoblastic leukemia (ALL) [244]”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [244]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“is overexpressed in retinoblastoma and esophageal carcinoma and its expression is directly correlated with tumor aggressiveness [271,272].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [271]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [272]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Yolanda’s group has shown that ectopic expression of miRNA-128 downregulated genes that induce apoptosis and upregulated genes implicated in cell survival [63].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [63]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that miRNA-128 reduces cell motility and invasiveness of tumor cells and thus prevents angiogenesis.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Donzelli et al. observed that miRNA-128-2 expression in lung cancer cells inhibits apoptosis and confers increased resistance to cisplatin, doxorubicin and 5-Fluorouracyl treatment via E2F5 (Figure 2) [266].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [266]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Synaptogenesis; reduces neuroblastoma cell motility and invasiveness; suppressor of PRC activity; renders glioma stemlike cells less radioresistant; suppressor of the colony formation ability and invasiveness of pituitary tumor cells; suppressor of growth and mediates differentiation; regulates Nonsense-mediated decay; regulates apoptosis, inhibits proliferation and self-renewal,”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MicroRNAs in brain development and function
What the sources say
- Not matchedcites [55]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [56]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [57]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [59]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [60]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [61]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [62]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [63]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [64]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“DCX is a microtubule-associated protein required for neuroblastic migration during cerebral cortex development [267]”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [267]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“raise the possibility of exploiting miRNA-128 for therapeutic intervention and development of novel therapies.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Future directions/conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“Reelin is a high-molecular-weight secreted glycoprotein, which is thought to play its role as a guide for migratory neurons [268].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [268]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Monteys et al. have recently suggested dual regulation of miRNA-128-2 by both intronic (pol III) and host gene (Pol II) promoters in acute lymphoblastic leukemia [283].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Future directions/conclusions
What the sources say
- Not matchedcites [283]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“alterations in miRNA expression may play a critical role in the cancer initiation and progression [255,256].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [255]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [256]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“MiRNA expression can be correlated with cancer type, stage, and other clinical variables which may be useful for the classification, diagnosis, or prognosis of some human malignancies [257].”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [257]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Alterations in susceptibility to apoptosis is a key factor for the survival of a malignant cell [261]”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Pro-neural miRNA-128 as regulator of apoptosis
What the sources say
- Not matchedcites [261]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Reelin has been shown to be a positive marker for prostate carcinoma aggressiveness [270]”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of miRNA-128 in cell motility, angiogenesis and senescence
What the sources say
- Not matchedcites [270]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“recent evidence indicates that miRNAs may function as tumor suppressors (by binding to oncogenes and suppressing them) or oncogenes (by binding to tumor suppressor genes and suppressing them)”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Expression of pro-neural miRNA-128 in cancers other than brain
What the sources say
- Not matchedcites [255]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [256]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that miRNA-128 plays multiple roles - a pro-apoptotic molecule, a anti-apoptotic molecule as well as a regulator of cholesterol homeostasis”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Future directions/conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper relies on this without support.
miRNA-128 is the most abundant brain-enriched miRNA.
“before delving into specific example of miRNA-128, the most abundant brain-enriched miRNA”
The paper relies on this without support.
miRNA-128 has tissue-specific and developmental-specific expression patterns.
“Evidences in the literature reveal that miRNA-128 has tissue specific and developmental specific expression patterns.”
The paper relies on this without support.
Apart from brain, miRNA-128 is found in skeletal muscle and thymus and is highly expressed during neuronal differentiation.
“Apart from brain, miRNA-128 has also been found in the skeletal muscle and thymus and is highly expressed during neuronal differentiation.”
The paper relies on this without support.
miRNAs normally negatively regulate their transcript targets.
“miRNAs normally negatively regulate their transcript targets”
The paper relies on this without support.
Cancer occurs due to accumulation of several genomic alterations and is characterized by unrestricted proliferation, invasion, and metastasis.
“Cancer occurs due to accumulation of several genomic alterations and is characterized by unrestricted proliferation, invasion, and metastasis.”
The paper relies on this without support.
MiRNA-128 is encoded by two distinct genes, R3HDM1 and ARPP21.
“MiRNA-128 is encoded by two distinct genes, viz., R3HDM1 and ARPP21.”
The paper relies on this without support.
The overall cellular functions and pathways affected by miRNA-128 remain undiscovered due to lack of high throughput target validation methods.
“The overall cellular functions and pathways affected by this miRNA remains still undiscovered due to lack of high throughput target validation methods.”
The paper relies on this without support.
Ability to migrate and disseminate to distal sites is one of the key characteristics of tumor cells, which is also responsible for the relative aggressiveness of the tumor.
“Ability to migrate and eventually disseminate to distal sites is one of the key characteristic of tumor cells, which is also responsible for the relative aggressiveness of the tumor.”
The paper relies on this without support.
Aberrant regulation of cholesterol homeostasis is associated with obesity as well as multiple types of cancer.
“Aberrant regulation of cholesterol homeostasis is associated with obesity as well as multiple types of cancer.”
The paper relies on this without support.
DCX expression is detectable in some tumors of the nervous system, such as GBM and neuroblastoma.
“DCX expression is also detectable in some tumors of the nervous system, such as GBM and neuroblastoma.”
The paper relies on this without support.
Overexpression of miRNA-128 leads to increased methylation of histone 3 lysine 9 (H3K9me2).
“Observation by Venkatraman’s group of increased methylation of histone 3 lysine 9 (H3K9me2) (a mark of repressed gene expression mediated by the Bmi-1 polycomb repressor complex) after overexpression of miRNA-128”
The paper relies on this without support.
Overexpression of miRNA-128a in medulloblastoma alters the intracellular redox state of the tumor cells.
“overexpression of miRNA-128a in medulloblastoma alters the intracellular redox state of the tumor cells.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
“| hsa-miRNA-128 | Glioma | d | [58] | 2008 |”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > References
“58. Zhang Y Chao T Li R Liu W Chen Y Yan X Gong Y Yin B Qiang B Zhao J Yuan J Peng X MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a J Mol Med (Berl) 2009 87 43 51”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > Role of pro-neural miRNA-128 in brain related disorders
“| hsa-miRNA-128 | Huntington’s disease | d | [241] | 2010 |”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > References
“241. Lee ST Chu K Im WS Yoon HJ Im JY Park JE Park KH Jung KH Lee SK Kim M Roh JK Altered microRNA regulation in Huntington’s disease models Exp Neurol 2011 227 172 179”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction
“MicroRNAs (miRNAs) interfere with target gene expression by binding to the 3′ UTRs of their target mRNAs and act primarily at the level of translation.”
§ Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 > Introduction > MiRNA biogenesis and mechanism of action
“However, it is now believed that miRNA regulate gene expression in majority of cases by mRNA decay rather than translational repression [47].”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“Chen Z Li D Cheng Q Ma Z Jiang B Peng R Chen R Cao Y Wan X MicroRNA-203 inhibits the proliferation and invasion of U251 glioblastoma cells by directly targeting PLD2 Mol Med Rep 2014 9 503 508 24270883”
Cited work 10.3892/mmr.2013.1814 · retracted 2023-12-27 · notice 10.3892/mmr.2023.13154 · this paper published 2014
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“10.1371/journal.pone.0055008”
Cited work 10.1371/journal.pone.0055008 · retracted 2020-01-23 · notice 10.1371/journal.pone.0228340 · this paper published 2014
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“10.1016/j.stem.2007.04.001”
Cited work 10.1016/j.stem.2007.04.001 · retracted 2023-06-01 · notice 10.1016/j.stem.2023.05.009 · this paper published 2014
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
Cited work 10.1111/cas.12351 · retracted 2024-07-22 · notice 10.1111/cas.16269 · this paper published 2014
Citations
Cites
4 retracted
Fasano, C. A., Dimos, J. T., Ivanova, N. B., Lowry, N. A., Lemischka, I. R., & Temple, S. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.04.001 · Cited by 308
RetractedYang, T., Lu, X., Wu, T., Ding, D.-D., Zhao, Z., Chen, G., Xie, X., Li, B., Wei, Y., Guo, L., et al. (2014) · Cancer Science · doi:10.1111/cas.12351 · Cited by 130
RetractedMiR-30a-5p Antisense Oligonucleotide Suppresses Glioma Cell Growth by Targeting SEPT7
Jia, Z., Wang, K., Wang, G., Zhang, A., & Pu, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055008 · Cited by 68
RetractedChen, Z., LI, D., Cheng, Q., Ma, Z., Jiang, B., Peng, R., Chen, R., Cao, Y., & Wan, X. H. (2013) · Molecular Medicine Reports · doi:10.3892/mmr.2013.1814 · Cited by 56
RetractedMicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
The 2007 WHO Classification of Tumours of the Central Nervous System
Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., Scheithauer, B. W., & Kleihues, P. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0243-4 · Cited by 15,675
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993) · Cell · doi:10.1016/0092-8674(93)90529-y · Cited by 12,948
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 9,051
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P. (2011) · Cell · doi:10.1016/j.cell.2011.07.014 · Cited by 7,262
Oncomirs—MicroRNAs with a role in cancer
Esquela-Kerscher, A., & Slack, F. J. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1840 · Cited by 5,884
Cited by
Sorted by citations
The potential of endurance exercise-derived exosomes to treat metabolic diseases
Safdar, A., Saleem, A., & Tarnopolsky, M. A. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.76 · Cited by 463
A rigorous method to enrich for exosomes from brain tissue
Vella, L. J., Scicluna, B. J., Cheng, L., Bawden, E., Masters, C. L., Ang, C., Williamson, N. A., McLean, C., Barnham, K. J., & Hill, A. F. (2017) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2017.1348885 · Cited by 321
Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?
Kumar, S., & Reddy, P. H. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.06.001 · Cited by 292
Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders
van den Berg, M. M. J., Krauskopf, J., Ramaekers, J. G., Kleinjans, J. C. S., Prickaerts, J., & Briedé, J. J. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101732 · Cited by 260
Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise
Safdar, A., & Tarnopolsky, M. A. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029827 · Cited by 203
Metadata
- Authors
- Adlakha, Y. K., & Saini, N.
- Affiliations
- Institute of Genomics and Integrative Biology (IN)
- Corresponding author
- Saini, Neeru
- Venue
- Molecular Cancer
- Published
- 2014
- Volume
- 13
- Issue
- 1
- Pages
- 33
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC3936914
- OpenAlex
- W2151668353
- Semantic Scholar
- 5e2e0380167b8a7d1673392477a8315e67cd3687
- Cited by
- 213
- References
- 287
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 14 · 2023: 23 · 2022: 23 · 2021: 13 · 2020: 31 · 2019: 20 · 2018: 14 · 2017: 23 · 2016: 21 · 2015: 9 · 2014: 1
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India (BSC 0123)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA, brain development, brain tumors, neuronal differentiation, miRNA target genes, apoptosis, angiogenesis, tumor progression, cholesterol metabolism, self-renewal, tumor invasion, miRNA-based therapy, metabolic disorders
- MeSH terms
- Animals, Brain, Gene Expression Regulation, Humans, Neoplasms, Apoptosis, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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