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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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“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
What the sources say
- Not matchedcites [277]
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In the paper
“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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In the paper
“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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“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
What the sources say
- Not matchedcites [57]
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In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“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
What the sources say
- Not matchedcites [57]
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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
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“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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- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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]
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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.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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]
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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]
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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.
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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.
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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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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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.
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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.
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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]
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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]
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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]
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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]
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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]
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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]
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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]
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Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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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]
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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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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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
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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]
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Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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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.
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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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]
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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]
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Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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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]
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Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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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]
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Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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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]
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Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably 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.
Huntington's disease study year differs from its reference
MinorTable 3 gives 2010 as the year for reference [241], while the reference list gives 2011.
“| hsa-miRNA-128 | Huntington’s disease | d | [241] | 2010 |”
“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”
Glioma study year differs from its reference
MinorTable 3 gives 2008 as the year for reference [58], while the reference list gives 2009.
“| hsa-miRNA-128 | Glioma | d | [58] | 2008 |”
“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”
Conflicting descriptions of the primary mechanism of miRNA regulation
MinorThe paper first says miRNAs act primarily at the level of translation, but later says that in the majority of cases they regulate expression through mRNA decay rather than translational repression.
“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.”
“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.
Cites a retracted work: 10.1016/j.stem.2007.04.001
InfoThe cited work was retracted on 2023-06-01 (notice 10.1016/j.stem.2023.05.009), not before this paper was published (2014).
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
“10.1016/j.stem.2007.04.001”
Cites a retracted work: 10.3892/mmr.2013.1814
InfoThe cited work was retracted on 2023-12-27 (notice 10.3892/mmr.2023.13154), not before this paper was published (2014).
Cited work 10.3892/mmr.2013.1814 · retracted 2023-12-27 · notice 10.3892/mmr.2023.13154 · this paper published 2014
Cites a retracted work: 10.1371/journal.pone.0055008
InfoThe cited work was retracted on 2020-01-23 (notice 10.1371/journal.pone.0228340), not before this paper was published (2014).
Cited work 10.1371/journal.pone.0055008 · retracted 2020-01-23 · notice 10.1371/journal.pone.0228340 · this paper published 2014
“10.1371/journal.pone.0055008”
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Downregulation of mi RNA ‐128 sensitises breast cancer cell to chemodrugs by targeting Bax
Ji, S., Shao, G., Lv, X., Liu, Y., Fan, Y., Wu, A., & Hu, H. (2013) · Cell Biology International · doi:10.1002/cbin.10100 · Cited by 25
Modulation of BK Channel by MicroRNA-9 in Neurons After Exposure to HIV and Methamphetamine
Tatro, E. T., Hefler, S., Shumaker-Armstrong, S., Soontornniyomkij, B., Yang, M., Yermanos, A., Wren, N., Moore, D. J., & Achim, C. L. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9446-8 · Cited by 24
Wang, S., Lu, S., Geng, S., Ma, S., Liang, Z., & Jiao, B. (2014) · Pathology & Oncology Research · doi:10.1007/s12253-013-9701-6 · Cited by 11
Flagged first, then by citations
1 of the 287 references couldn’t be matched to a known paper.
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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