MiR-128-3p – a gray eminence of the human central nervous system

In the paper

“High-throughput genomic, epigenomic, and transcriptomic profiling of glioblastoma cells revealed three main subtypes harboring distinct molecular and phenotypic landscapes that affect response to the therapy and clinical outcome: mesenchymal, proneural, and classical subtypes.96,97,98,99,100”

What the sources say

• Disputed

  Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  cites [96] Verhaak, 2010, Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1, Cancer Cell sourceExperimental — accuracy not yet measured
• Disputed

  Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  cites [97] Brennan, 2013, The Somatic Genomic Landscape of Glioblastoma, Cell sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [98] Frattini, 2013, The integrated landscape of driver genomic alterations in glioblastoma, Nat. Genet. sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [99] Neftel, 2019, An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma, Cell sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [100] Wang, 2021, Proteogenomic and metabolomic characterization of human glioblastoma, Cancer Cell sourceExperimental — accuracy not yet measured

In the paper

“the antagomir-mediated depletion of miR-128-2 promoted neuronal cell cycle re-entry and exacerbated ischemia reperfusion-induced neuronal injury.66”

What the sources say

• Partly supported

  The Results section reports that a miR-128 antagomir increased cell-cycle re-entry and aggravated injury in primary neurons exposed to oxygen-glucose deprivation/reoxygenation, an in vitro model of ischemia-reperfusion. The paper does not establish that the antagomir specifically depleted miR-128-2; its Introduction identifies miR-128-1 and miR-128-2 as separate genes. (LLM, conf=0.88)

  cites [66] Liu, 2019, Upregulation of MicroRNA-128 in the Peripheral Blood of Acute Ischemic Stroke Patients is Correlated with Stroke Severity Partially through Inhibition of Neuronal Cell Cycle Reentry, Cell Transplant. sourceExperimental — accuracy not yet measured

In the paper

“Parkinson’s disease (PD) is a neurodegenerative disorder resulting in severe disability due to progressive degeneration of the nigrostriatal dopaminergic pathway.60,61”

What the sources say

• ?Not checked — no full text of the sourcecites [60] Kalia, 2015, Parkinson’s disease, Lancet Lond. Engl. source
• Partly supported

  The Introduction identifies Parkinson’s disease as a progressive neurodegenerative disease, and Neuropathology describes degeneration of substantia nigra dopaminergic neurons and loss of dopaminergic terminals associated with motor symptoms. These passages do not establish the claim’s stronger assertion that this degeneration results in severe disability; the Introduction also notes pathology beyond the dopaminergic system. Page numbers were not available in our copy. (LLM, conf=0.82)

  cites [61] Simon, 2020, Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology, Clin. Geriatr. Med. sourceExperimental — accuracy not yet measured

In the paper

“A large volume of evidence implicates microRNAs playing crucial roles in multiple biological functions such as proliferation, differentiation, or apoptosis.3,21”

What the sources say

• Partly supported

  The Introduction says miRNAs are involved in a variety of biological processes. The section on cellular miRNA actions discusses differentiation, and the section on secretion and uptake describes miRNA-promoted fibroblast proliferation. I found no passage in our copy linking miRNAs to apoptosis, so that example is not supported. (LLM, conf=0.84)

  cites [3] O’Brien, 2018, Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation, Front. Endocrinol. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [21] Saliminejad, 2019, An overview of microRNAs: Biology, functions, therapeutics, and analysis methods, J. Cell. Physiol. source

In the paper

“Crucially, although both ∼80-nucleotide-long pre-miR-128 form different stem-loop structures, they yield identical mature miR-128-3p after processing by DICER.1,23,26”

What the sources say

• Partly supported

  The Single Cleavage Pre-miRNA Processing section (page unavailable) says Dicer processes precursor hairpins into miRNA duplexes. The Intergenic microRNA section describes precursor hairpins generally, but neither passage establishes that there are two distinct ∼80-nucleotide pre-miR-128 hairpins or that both yield identical mature miR-128-3p. (LLM, conf=0.86)

  cites [1] MacFarlane, 2010, MicroRNA: Biogenesis, Function and Role in Cancer, Curr. Genomics sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [23] Kim, 2009, Biogenesis of small RNAs in animals, Nat. Rev. Mol. Cell Biol. source
• ?Not checked — no full text of the sourcecites [26] Kim, 2005, MicroRNA biogenesis: coordinated cropping and dicing, Nat. Rev. Mol. Cell Biol. source

In the paper

“Overexpression of miR-128-3p has inhibited apoptosis of neurons, inflammation, and improved motor function following SCI via down-regulation of serine/threonine-protein kinase ULK1 and elevation of Fas ligand (FasL).57”

What the sources say

• Partly supported

  The Discussion reports reduced neuronal apoptosis and inflammation and improved motor function after miR-128 overexpression, and one Discussion sentence describes FasL elevation. However, the Results report significantly lowered FasL after ULK1 silencing, and the Abstract concludes that miR-128 attenuates SCI through FasL downregulation. The claimed direction of the FasL effect is therefore inconsistent with the paper’s reported findings and conclusion. (LLM, conf=0.88)

  cites [57] Liu, 2021, Upregulation of miR-128 inhibits neuronal cell apoptosis following spinal cord injury via FasL downregulation by repressing ULK1, Mol. Med. Rep. sourceExperimental — accuracy not yet measured

In the paper

“Regarding proliferation and differentiation, miR-128-3p targets genes like RELN (Reelin)141 and PHF6,37 impacting neuronal migration, layer formation, and neurite outgrowth.”

What the sources say

• Partly supported

  The Abstract and Discussion (pages unavailable) identify Reelin/RELN as a miR-128 target involved in neuronal migration. They do not establish that miR-128 targeting RELN affects layer formation or neurite outgrowth; the reported neurite measurements concern retinoic-acid-treated cells. PHF6 has a separate citation in the citing sentence and is not attributed to this paper. (LLM, conf=0.85)

  cites [141] Evangelisti, 2009, MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness, FASEB J sourceExperimental — accuracy not yet measured
• Supported

  The Results section identifies Phf6 as a miR-128 target and shows that restoring PHF6 alleviates the neuronal migration defect. The Discussion links miR-128 regulation of PHF6 to cortical lamination, while the Results show PHF6 counteracts miR-128’s effect on dendritic complexity. RELN has a separate citation in the citing sentence and is not attributed to this source. (LLM, conf=0.92)

  cites [37] Franzoni, 2015, miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6, Elife source

In the paper

“Aberrations in PRCs’ functionality were linked to several human cancers,120,121 significantly contributing to the self-renewal/differentiation balance of cancer stem cells,122,123,124 including GSCs.125”

What the sources say

• Partly supported

  The review links altered Polycomb-group activity to multiple cancers (PcG proteins and cancer, p. 5) and says these proteins help maintain cancer stem-cell populations (p. 4). It also proposes that aberrant Polycomb-mediated repression may block differentiation (p. 5). The cited passages do not establish the claim specifically for glioma stem cells (GSCs), and the proposed differentiation mechanism is less certain than the citing sentence suggests. (LLM, conf=0.85)

  cites [120] Bracken, 2009, Polycomb group proteins: navigators of lineage pathways led astray in cancer, Nat. Rev. Cancer sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [121] Pasini, 2016, Emerging roles for Polycomb proteins in cancer, Curr. Opin. Genet. Dev. source
• Supported

  The source’s Abstract says deregulated PRC2 activity is frequent in human tumors, and the passage on PRC2 genes describes their deregulation in several cancers. This supports the first clause, to which citations 120–121 are attached; the cancer-stem-cell and GSC clauses have separate citations and are not attributed to this source. (LLM, conf=0.93)

  cites [122] Pasini, 2004, Polycomb group proteins in cell cycle progression and cancer, Cell Cycle source
• Partly supported

  The Concluding Remarks link aberrant Polycomb-group complex activity to human tumors and cancer stem cell biology, while the Abstract describes roles in stem cell self-renewal and differentiation. The passages found do not establish the claimed self-renewal/differentiation balance specifically in glioma stem cells (GSCs); the glioma passage concerns proliferation and self-renewal, not that balance. (LLM, conf=0.82)

  cites [123] Sauvageau, 2010, Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer, Cell Stem Cell sourceExperimental — accuracy not yet measured
• Supported

  The Abstract links Polycomb misregulation to multiple cancers and to cancer stem cells with increased self-renewal and incomplete differentiation. The “Polycomb Proteins and Cancer” section specifically reports that altering EZH2 or Bmi-1 levels reduces self-renewal in glioblastoma or glioma stem cells. Page numbers were not supplied. (LLM, conf=0.92)

  cites [124] Richly, 2011, Roles of the Polycomb group proteins in stem cells and cancer, Cell Death Dis. source
• ?Not checked — no full text of the sourcecites [125] Bian, 2014, Epigenetic modification in gliomas: role of the histone methyltransferase EZH2, Expert Opin. Ther. Targets source

In the paper

“Crucially, the levels of miR-128-3p forms can also differ depending on the genetic and molecular background, as they correlated with the glioblastoma subtypes, with the most reduced expression in the most aggressive mesenchymal one.96,113”

What the sources say

• Partly supported

  The Results (Functional Annotation of Subtypes) and Discussion describe genetically distinct glioblastoma subtypes, including a Mesenchymal subtype associated with NF1 abnormalities. They do not report miR-128-3p expression by subtype or establish that its expression is lowest in Mesenchymal tumors. The cited passages also do not call Mesenchymal the most aggressive subtype. (LLM, conf=0.81)

  cites [96] Verhaak, 2010, Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1, Cancer Cell sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section ('miR-128 is repressed in gliomas'; page unavailable) reports that miR-128-1 expression differs among glioblastoma subtypes, distinguishing less aggressive Neural/Pro-Neural tumors from aggressive Classical and Mesenchymal tumors. It specifically reports reduced expression in Classical relative to Neural tumors, but does not establish that miR-128-3p forms are lowest in the Mesenchymal subtype. (LLM, conf=0.87)

  cites [113] Papagiannakopoulos, 2012, Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases, Oncogene sourceExperimental — accuracy not yet measured

In the paper

“Additionally, miR-128-3p targets synaptic plasticity and memory-related genes, such as CREB1 (CAMP Responsive element binding protein 1) or NRXN1 (Neurexin 1),142 and genes encoding subunits of ion channels and transporters like the Big Potassium (BK) channel.29”

What the sources say

• ?Could not verify

  The Discussion describes CREB as acting upstream of MEG3 and identifies JAG1 as a miR-128-3p target. Our copy does not say that miR-128-3p targets CREB1, NRXN1, or the BK channel, or link those targets to synaptic plasticity and memory (searched: CREB1, NRXN1, BK channel, ion channel subunits). (LLM, conf=0.74)

  cites [142] Gao, 2019, Long Non-coding RNA Maternally Expressed 3 Increases the Expression of Neuron-Specific Genes by Targeting miR-128-3p in All-Trans Retinoic Acid-Induced Neurogenic Differentiation From Amniotic Epithelial Cells, Front. Cell Dev. Biol. sourceExperimental — accuracy not yet measured
• Partly supported

  The passage on miR-128 target genes (section labeled Abstract; page unavailable) says miR-128 regulates numerous ion channels and transporters. It does not identify the BK channel among them. The CREB1 and NRXN1 examples carry a different citation in the citing sentence and are not assessed here. (LLM, conf=0.86)

  cites [29] Tan, 2013, MicroRNA-128 Governs Neuronal Excitability and Motor Behavior in Mice, Science sourceExperimental — accuracy not yet measured

In the paper

“Overexpression of miR-128-3p considerably increased the percentages of DCs, CD8+ T cells, and natural killer T cells (NKT) within the tumor and spleen.”

• Also stated in: § Cancers · plain

  “Therefore, a significantly enhanced antitumor response was observed.177”

What the sources say

• Supported

  The Results section, “Overexpression of miR-128 Enhanced Anti-tumor Immunity in PDAC” (page unavailable), reports increased percentages of DCs, CD8+ T cells, and NKT cells in both tumors and spleens of mice bearing miR-128-overexpressing tumors. It concludes that miR-128 overexpression could enhance anti-tumor immunity. (LLM, conf=0.90)

  cites [177] Xi, 2020, miR-128 Regulates Tumor Cell CD47 Expression and Promotes Anti-tumor Immunity in Pancreatic Cancer, Front. Immunol. source

In the paper

“Overall, these modifications contribute to prolonged circulation in the bloodstream and improved delivery to the CNS.190”

What the sources say

• Partly supported

  The Phosphonate modification section (page unavailable) says phosphorothioate modification may prolong circulation time. The Other platforms section (page unavailable) describes CNS-targeted delivery using lipophilic siRNA conjugates. The paper supports the two effects separately, but does not establish that the same modifications produce both. (LLM, conf=0.82)

  cites [190] Hu, 2020, Therapeutic siRNA: state of the art, Signal Transduct. Target. Ther. sourceExperimental — accuracy not yet measured

In the paper

“Some ASOs were clinically approved for certain neuromuscular diseases and are currently in trials for other conditions.184,185”

What the sources say

• Supported

  The Mechanisms of action section says nusinersen and eteplirsen were approved in 2016 for spinal muscular atrophy and Duchenne muscular dystrophy, respectively. The Exon-skipping ODNs section and the ALS section describe other oligonucleotide therapies in clinical development and trials (page numbers unavailable). (LLM, conf=0.94)

  cites [184] Khorkova, 2017, Oligonucleotide therapies for disorders of the nervous system, Nat. Biotechnol. source
• ?Not checked — no full text of the sourcecites [185] Levin, 2019, Treating Disease at the RNA Level with Oligonucleotides, N. Engl. J. Med. source

In the paper

“They are small molecules frequently conserved among species208 that are remarkably stable in plasma and serum due to high resistance to RNase activity and degradation.209”

What the sources say

• Supported

  The Introduction describes miRNAs as small molecules that are often conserved among species, supporting the clause attached to citation 208. The plasma-and-serum stability clause is attached to citation 209, not to this source. (LLM, conf=0.94)

  cites [208] Christopher, 2016, MicroRNA therapeutics: Discovering novel targets and developing specific therapy, Perspect. Clin. Res. source
• Supported

  The Introduction states that miRNAs are remarkably stable in plasma and serum and resistant to RNase activity. This supports the stability claim attached to citation 209; the separate claim about conservation among species is attached to citation 208. (LLM, conf=0.90)

  cites [209] Glinge, 2017, Stability of Circulating Blood-Based MicroRNAs - Pre-Analytic Methodological Considerations, PLoS One source

In the paper

“The delivery of therapeutic RNA molecules (siRNA or microRNA) encapsulated within the lipid or lipid-like carrier231,232 into the cells or tissues was proven to be effective in infectious diseases and tumors, as shown in many preclinical studies233,234,235 and clinical trials (reviewed by Kaczmarek et al.236).”

What the sources say

• ?Not checked — no full text of the sourcecites [231] Akinc, 2008, A combinatorial library of lipid-like materials for delivery of RNAi therapeutics, Nat. Biotechnol. source
• Supported

  The citation is attached to the lipid or lipid-like carrier, not to the later claim about effectiveness against infectious diseases and tumors. The Discussion (page not supplied) describes this paper’s lipidoid-based formulation for delivering siRNA to hepatocytes in vivo, so it supports the carrier identification. (LLM, conf=0.91)

  cites [232] Akinc, 2009, Development of lipidoid-siRNA formulations for systemic delivery to the liver, Mol. Ther. source
• Supported

  The Discussion describes lipopeptide nanoparticles composed of lipopeptides, phospholipids, PEG-lipid, cholesterol, and siRNA, and says they improved siRNA delivery. This source supports the carrier example for which citations 231–232 are placed; the sentence assigns the infectious-disease and tumor efficacy claim to later citations. (LLM, conf=0.90)

  cites [233] Dong, 2014, Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates, Proc. Natl. Acad. Sci. source
• ?Not checked — no full text of the sourcecites [234] Kauffman, 2015, Optimization of Lipid Nanoparticle Formulations for mRNA Delivery in Vivo with Fractional Factorial and Definitive Screening Designs, Nano Lett. source
• Supported

  This citation is attached to “lipid or lipid-like carrier,” not to the later claim about efficacy against infectious diseases and tumors. The paper describes ionizable lipids formulated into lipid nanoparticles to deliver RNA in vivo (passages 2–3, section labeled Abstract), so it supports the carrier identification. Its experiments concern mRNA delivery, not disease-treatment outcomes. (LLM, conf=0.90)

  cites [235] Fenton, 2016, Bioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery, Adv. Mater. source
• Partly supported

  The Delivery materials section describes lipid and lipid-like carriers as effective RNA-delivery vehicles, and Table 2 lists lipid-nanoparticle siRNA trials for several cancers. The Protein downregulation section reports lipid-nanoparticle microRNA treatment in a mouse model of colorectal cancer, but says the liposomal microRNA cancer trial was terminated after severe adverse events. These passages do not establish proven clinical effectiveness against tumors, and the reviewed passages do not show effectiveness of lipid-carried siRNA or microRNA against infectious diseases. (LLM, conf=0.86)

  cites Kaczmarek et al. [236] Kaczmarek, 2017, Advances in the delivery of RNA therapeutics: from concept to clinical reality, Genome Med. sourceExperimental — accuracy not yet measured

In the paper

“These modifications can enhance the ability of EVs to selectively bind to specific cell types or tissues, thereby reducing off-target delivery and increasing the therapeutic potential of the encapsulated cargo,215,216 including in cancer217,218 and CNS pathologies.219,220”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [215] Zhao, 2016, Multifunctional Transmembrane Protein Ligands for Cell-Specific Targeting of Plasma Membrane-Derived Vesicles, Small source
• Supported

  In “Bioengineering of EVs > Methods of preparation and engineering of engineered EVs and EV-mimetics” (page unavailable), the review says surface modification can improve EV targeting efficiency and gives examples of specific delivery to neurons and glia and targeting of tumor cells. Its “Engineered EVs” section says such modifications are intended to enhance delivery of therapeutic contents. Reduced off-target delivery is a reasonable implication of the improved targeting described, rather than a separately measured outcome in these passages. (LLM, conf=0.85)

  cites [216] Sil, 2020, Strategies for the use of Extracellular Vesicles for the Delivery of Therapeutics, J. Neuroimmune Pharmacol. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [217] Bellavia, 2017, Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth, Theranostics source

In the paper

“Nusinersen is designed to modify the splicing of the SMN2 (Survival of motor neuron 2, centromeric) gene, increasing the production of functional SMN protein.184,186,187”

What the sources say

• Supported

  The SMA section states that nusinersen blocks splicing repressors at an SMN2 intron, leading to exon 7 inclusion and increased production of full-length SMN2 protein. This supports the claim that it modifies SMN2 splicing to increase functional SMN protein. (LLM, conf=0.94)

  cites [184] Khorkova, 2017, Oligonucleotide therapies for disorders of the nervous system, Nat. Biotechnol. source
• Supported

  The Introduction’s pharmacology table describes nusinersen altering SMN2 pre-mRNA splicing so that exon 7 is retained and functional SMN protein is produced. The clinical considerations section likewise states that it increases full-length SMN protein levels. (LLM, conf=0.94)

  cites [186] Hoy, 2021, Nusinersen: A Review in 5q Spinal Muscular Atrophy, CNS Drugs source
• Supported

  The ‘Nusinersen and preclinical discovery’ section explains that antisense oligonucleotides targeting a splicing-silencer region in SMN2 pre-mRNA promote exon 7 inclusion and production of full-length SMN protein. The same section identifies nusinersen as an antisense oligonucleotide designed to increase expression of that protein, supporting the claimed mechanism. (LLM, conf=0.93)

  cites [187] Gidaro, 2019, Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps, Dev. Med. Child Neurol. source

In the paper

“Diverse strategies in other CNS disease therapies utilize microRNA inhibitors,188 mimics,189 siRNAs,190 and ASOs191 to modulate treatment efficacy.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [188] Zhang, 2013, Progress in microRNA delivery, J. Control. Release source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [189] Sun, 2018, MicroRNA-based therapeutics in central nervous system injuries, J. Cereb. Blood Flow Metab. source
• Supported

  Citation 190 is attached to the siRNA portion of the sentence, not the separately cited microRNA or ASO portions. In “siRNA delivery and drug development > Other platforms” (page not provided), the review describes CNS-targeted siRNA delivery and gene silencing in brain tissue as developments that extend the diseases treatable by RNAi therapeutics. (LLM, conf=0.88)

  cites [190] Hu, 2020, Therapeutic siRNA: state of the art, Signal Transduct. Target. Ther. source

In the paper

“EVs, as the naturally secreted carriers of functional biomolecules (nucleic acids: genomic DNA, cDNA; RNAs: mRNA, microRNA, lncRNA; proteins and lipids)212 have recently attracted much attention as potentially useful nano-tools for transferring therapeutic agents, including microRNAs.”

What the sources say

• Partly supported

  Section 4.3 (page unavailable) says extracellular vesicles naturally deliver genomic DNA, mRNA, miRNA and other noncoding RNAs, and discusses their use as nucleic-acid carriers. Section 4 (page unavailable) also describes them as nanoscale drug-delivery systems. The cited passages do not establish the specific claims that they naturally carry cDNA or have been used to transfer therapeutic microRNAs; the therapeutic RNA examples concern siRNA and antisense RNA targeting a microRNA. (LLM, conf=0.83)

  cites [212] Palazzolo, 2020, Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools, Cancers sourceExperimental — accuracy not yet measured

In the paper

“Furthermore, molecules encapsulated within blood-circulating EVs may also serve as diagnostic, prognostic, and predictive biomarkers.222,223”

What the sources say

• Partly supported

  The introduction (p. 2) says EVs enclose proteins and RNA and that their use as biomarkers in various diseases is being explored. The Discussion (p. 9) also considers the biomarker value of circulating components in biological fluids. Neither passage specifically establishes that molecules within blood-circulating EVs serve as diagnostic, prognostic, and predictive biomarkers. (LLM, conf=0.85)

  cites [222] Kowal, 2016, Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes, Proc. Natl. Acad. Sci. sourceExperimental — accuracy not yet measured
• ?Could not verify

  The paper’s “Extracellular Vesicles: Next Generation Drug Delivery System?” section discusses EVs as carriers of biomolecules and therapeutic cargo, but does not address their use as diagnostic, prognostic, or predictive biomarkers in blood. Searches for those biomarker terms found only a diagnostic-biomarker phrase in a cited work’s title in the References, not a discussion of the claim in this paper. (LLM, conf=0.76)

  cites [223] Armstrong, 2018, Strategic design of extracellular vesicle drug delivery systems, Adv. Drug Deliv. Rev. sourceExperimental — accuracy not yet measured

In the paper

“The U.S. Food and Drug Administration approved the first CNS-related oligonucleotide-based drug, Nusinersen, for treating spinal muscular atrophy caused by a survival motor neuron (SMN) protein deficiency.”

What the sources say

• Supported

  The SMA section states that the disease is caused by reduced SMN1 protein and identifies nusinersen as an oligonucleotide designed to increase full-length SMN protein production. The same section says that the FDA approved nusinersen in December 2016 after discussing its trials in infants with SMA. (LLM, conf=0.93)

  cites [184] Khorkova, 2017, Oligonucleotide therapies for disorders of the nervous system, Nat. Biotechnol. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [186] Hoy, 2021, Nusinersen: A Review in 5q Spinal Muscular Atrophy, CNS Drugs source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [187] Gidaro, 2019, Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps, Dev. Med. Child Neurol. source

In the paper

“while the expression of R3HDM1 is particularly high in the cerebral cortex, where it overlaps with high levels of miR-128-3p (Figures S1B and S1C), ARPP21 is strongly expressed in basal ganglia.27”

What the sources say

• ?Not checked — no full text of the sourcecites [27] Sjöstedt, 2020, An atlas of the protein-coding genes in the human, pig, and mouse brain, Science source

In the paper

“MiR-128-3p, encoded by two separate genes, hsa-MIR128-1 and hsa-MIR128-2 (www.ensembl.org), is one of the most highly expressed microRNAs across the CNS and surroundings tissues (Figure 2).22”

• Also stated in: § MiR-128-3p biogenesis · plain

  “while miR-128-3p is one of the most enriched in the brain”

• Also stated in: § Abstract · plain

  “which is enriched in the brain”

What the sources say

• Not checked yetcites [22] Shao, 2010, Comprehensive survey of human brain microRNA by deep sequencing, BMC Genom. source

In the paper

“as this miRNA is a crucial regulator of gene expression in the brain, playing an essential role in the maintenance and function of cells stemming from neuronal lineage”

In the paper

“MicroRNAs are small (20–23 nucleotides), frequently highly conserved regulatory non-coding RNAs (ncRNA) that control post-transcriptional regulation of the expression of protein-coding genes.1”

What the sources say

• Not checked yetcites [1] MacFarlane, 2010, MicroRNA: Biogenesis, Function and Role in Cancer, Curr. Genomics source

In the paper

“MiR-128-3p also diminished the level/activity of such factors as tumor necrosis factor (TNF-α), interleukin-1β, interleukin-6, p38 mitogen-activated protein kinase (MAPK), or zinc finger E-box binding homeobox 1 (ZEB1) (in microglia)”

What the sources say

• ?Not checked — no full text of the sourcecites [59] Zhang, 2020, MicroRNA-128-3p Alleviates Neuropathic Pain Through Targeting ZEB1, Neurosci. Lett. source

In the paper

“This regulation promoted neurogenesis while inhibiting proliferation in the developing neocortex”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [33] Zhang, 2016, MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex, Elife source

In the paper

“MiR-128-3p, encoded by two separate genes, hsa-MIR128-1 and hsa-MIR128-2 (www.ensembl.org)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites www.ensembl.org

In the paper

“which are critical for maintaining the electrical activity of neurons that contribute to neuronal excitability and neurotransmitter-driven motor activity.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [29] Tan, 2013, MicroRNA-128 Governs Neuronal Excitability and Motor Behavior in Mice, Science source

In the paper

“Spinal cord injury (SCI) leads to permanent motor deficits accompanied by inflammation and oxidative stress, thus resulting in neuronal cell death.55,56”

What the sources say

• ?Not checked — no full text of the sourcecites [55] Ahuja, 2017, Traumatic spinal cord injury, Nat. Rev. Dis. Primers source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [56] Anjum, 2020, Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms, Int. J. Mol. Sci. source

In the paper

“while removal of miR-128-3p enhanced cell division, reducing neuron formation.33”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [33] Zhang, 2016, MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex, Elife source

In the paper

“Hsa-MIR128-1 is embedded within the intron of protein-coding gene R3HDM1 on chromosome 2 (q21.3), while hsa-MIR128-2 is located in chromosome 3 (p22.3) within the intron of the protein-coding ARPP-21 gene26”

What the sources say

• ?Not checked — no full text of the sourcecites [26] Kim, 2005, MicroRNA biogenesis: coordinated cropping and dicing, Nat. Rev. Mol. Cell Biol. source

In the paper

“The biogenesis of the hsa-MIR128-1 pathway is the canonical one and is regulated by polymerase II (Pol II), yet both can modulate the hsa-MIR128-2 pathway: Pol II host gene promotors and Pol III intronic promotors.24,25”

What the sources say

• ?Not checked — no full text of the sourcecites [24] Zeng, 2006, Principles of micro-RNA production and maturation, Oncogene source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [25] Monteys, 2010, Structure and activity of putative intronic miRNA promoters, RNA N. Y. N source

In the paper

“Its involvement spans neural progenitor cell regulation to orchestrating the formation of complex neuronal networks during brain circuit development.”

In the paper

“Interestingly, Tan et al. demonstrated that the mmu-MIR128-2 locus is responsible for generating a majority of mature mmu-miR-128-3p in mice29”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [29] Tan, 2013, MicroRNA-128 Governs Neuronal Excitability and Motor Behavior in Mice, Science source

In the paper

“Its reintroduction into pituitary cancer cells inhibits their colony-forming ability and invasiveness in vitro.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [74] Palumbo, 2013, Functional screen analysis reveals miR-26b and miR-128 as central regulators of pituitary somatomammotrophic tumor growth through activation of the PTEN–AKT pathway, Oncogene source

In the paper

“Reduced viability and neurosphere formation in vitro, decreased tumor burden and improved survival in the mouse intracranial xenograft model were observed due to this inter-subtype transition.130”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [130] Rooj, 2017, MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells, Cell Rep. source

In the paper

“Reintroducing miR-128-3p into medulloblastoma cells inhibited their growth in vitro by increasing the level of reactive oxygen species (ROS) and promoting cellular senescence through targeting a proto-oncogene BMI1 (B cell-specific Moloney murine leukemia virus integration site 1).82”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [82] Venkataraman, 2010, MicroRNA 128a Increases Intracellular ROS Level by Targeting Bmi-1 and Inhibits Medulloblastoma Cancer Cell Growth by Promoting Senescence, PLoS One source

In the paper

“The direct targeting of both PRCs by miR-128-3p leads to chromatin re-arrangements, followed by the reprogramming of PRC-dependent genes involved in the enforcement of the stemness program and inter-subclasses transition of brain tumor cells.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [130] Rooj, 2017, MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells, Cell Rep. source

In the paper

“In contrast to the neurodegeneration processes we described above, miR-128-3p was significantly down-regulated, and its overexpression was not observed in human malignant tumors of the CNS (summarized in Table 2), possibly due to different targeted genes, depending on the context of disorders and cell/tissue types.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 2

In the paper

“miR-128-3p plays a crucial role in developing CNS and maintaining its physiological functions.”

In the paper

“As the functional consequences of miR-128-3p,77,126 re-establishment and repression of PRCs subunits, pronounced alterations in histone modifications,77 as well as loss of stem-like features by GSCs, were observed in vitro and in vivo, as clearly shown by down-regulation of CD133 (Prominin-1) expression.77,126”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [77] Peruzzi, 2013, MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells, Neuro Oncol. source
• ?Not checked — no full text of the sourcecites [126] Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal, Cancer Res. source

In the paper

“They are considered tumor-initiating cells that render cancer resistant to conventional anti-glioblastoma therapies,90,91,92,93 leading to inevitable recurrence and fatal outcomes.94,95”

What the sources say

• ?Not checked — no full text of the sourcecites [90] Singh, 2003, Identification of a Cancer Stem Cell in Human Brain Tumors, Cancer Res.
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [91] Lathia, 2015, Cancer stem cells in glioblastoma, Genes Dev. source
• Not checked yet

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  cites [92] Yi, 2016, Glioblastoma Stem-Like Cells: Characteristics, Microenvironment, and Therapy, Front. Pharmacol. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [93] Król, 2020, Aberrantly Expressed RECQL4 Helicase Supports Proliferation and Drug Resistance of Human Glioma Cells and Glioma Stem Cells, Cancers source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [94] Gimple, 2019, Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer, Genes Dev. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [95] Prager, 2020, Glioblastoma Stem Cells: Driving Resilience through Chaos, Trends Cancer source

In the paper

“Reduced viability and neurosphere formation in vitro, decreased tumor burden and improved survival in the mouse intracranial xenograft model were observed due to this inter-subtype transition.130”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [130] Rooj, 2017, MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells, Cell Rep. source

In the paper

“Abundantly expressed in the human brain (primarily in neurons)”

In the paper

“As the functional consequences of miR-128-3p,77,126 re-establishment and repression of PRCs subunits, pronounced alterations in histone modifications,77 as well as loss of stem-like features by GSCs, were observed in vitro and in vivo, as clearly shown by down-regulation of CD133 (Prominin-1) expression.77,126”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [77] Peruzzi, 2013, MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells, Neuro Oncol. source
• ?Not checked — no full text of the sourcecites [126] Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal, Cancer Res. source

In the paper

“The reintroduction of miR-128-3p77,126 significantly inhibited the radiation-induced expression of PRC subunits and consequently enhanced the radiosensitivity of GSCs accompanied by substantial DNA damage.77,126”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [77] Peruzzi, 2013, MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells, Neuro Oncol. source
• ?Not checked — no full text of the sourcecites [126] Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal, Cancer Res. source

In the paper

“MiR-128-3p controls critical steps in committing toward neuronal lineage and maturing into terminally differentiated neurons, inhibiting cell migration or proliferation.”

In the paper

“MiR-128-3p was also involved in inhibiting Th2 development and promoting the differentiation of pro-inflammatory Th1 responses in patients with MS”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [69] Guerau-de-Arellano, 2011, Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity, Brain source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [70] Severin, 2016, MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis, Brain source

In the paper

“Several reports demonstrated the high level of miR-128-3p as a pro-inflammatory and anti-immunosuppressive factor in immune cells, potentially significantly enhancing antitumor immunity.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [176] Liang, 2017, miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of p38, Mol. Med. Rep. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [177] Xi, 2020, miR-128 Regulates Tumor Cell CD47 Expression and Promotes Anti-tumor Immunity in Pancreatic Cancer, Front. Immunol. source

In the paper

“and indirect interactions (microRNAs indirectly influence each other’s expression through affecting signaling pathways and other regulatory molecules156)”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [156] Mitra, 2020, Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival, Nat. Commun. source

In the paper

“The sponging of miR-128-3p by lncRNA Peg13 (Paternally expressed 13) resulted in a maintained expression of SOX13 (SRY-box transcription factor 13) and significantly reduced anesthetic-related neurotoxicity for NSCs in mice.174”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [174] Jiang, 2020, Long non-coding RNA Peg13 attenuates the sevoflurane toxicity against neural stem cells by sponging microRNA-128-3p to preserve Sox13 expression, PLoS One source

In the paper

“Overexpression of miR-128-3p diminished expression and secretion of IL-6 and IL-10 and increased IL-12, modifying the immune response in PD individuals.62”

What the sources say

• ?Not checked — no full text of the sourcecites [62] Zhou, 2018, MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson’s Disease by Binding to AXIN1, Cell. Physiol. Biochem. source

In the paper

“In this network, besides miR-128-3p, miR-9 and miR-124-3p target and repress the expression of USP14 (Ubiquitin specific peptidase 14) whose product interacts with and stabilizes EZH2, thereby allowing the repression of EZH2 and the consequent destabilization of REST.160”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [160] Lee, 2018, MicroRNAs Overcome Cell Fate Barrier by Reducing EZH2-Controlled REST Stability during Neuronal Conversion of Human Adult Fibroblasts, Dev. Cell source

In the paper

“Conversely, miR-128-3p targets numerous factors that maintain the”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [144] Ghersi, 2023, Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium, Nat. Cell Biol. source

In the paper

“Thus, the therapeutic usage of miR-128-3p is not without controversy, as it exhibits divergent effects depending on specific contexts and target co-expression genes and thus can be regarded as a”

In the paper

“Similarly, the binding sites for lncRNA LINC00346 within miR-128-3p have also been identified in glioma cells, and this regulatory network has enhanced tumor progression.166”

What the sources say

• ?Not checked — no full text of the sourcecites [166] Geng, 2020, Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma, Eur. Rev. Med. Pharmacol. Sci. source

In the paper

“These data indicate that miR-128-3p acts hand-in-hand with some transcriptional regulators while controlling some of them directly, suggesting a multilayered network of co-dependencies, most often in the context of neuronal tissues.”

In the paper

“It is also noteworthy that microRNAs can interact with other classes of non-coding RNAs as competing endogenous molecules.146,147”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [146] Salzman, 2012, Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types, PLoS One source
• ?Not checked — no full text of the sourcecites [147] Hansen, 2013, Natural RNA circles function as efficient microRNA sponges, Nature source

In the paper

“It thus becomes part of the consensus in the field that lncRNAs regulate the activity of many microRNAs, and the interplay between these types of ncRNAs is considered an emerging regulatory network essential for transcriptome regulation in physiological and pathological conditions.”

In the paper

“a brain tumor suppressor162”

What the sources say

• ?Not checked — no full text of the sourcecites [162] Li, 2021, The comprehensive landscape of miR-34a in cancer research, Cancer Metastasis Rev. source

In the paper

“Similarly, the multitude of putative and experimentally confirmed target mRNAs include both tumor-suppressive and pro-oncogenic genes, rendering the ultimate effect uncertain.”

In the paper

“Consequently, the differentiation of Th2 cells was inhibited, while the pro-inflammatory activity of T helper type 1 (Th1) cells was promoted, resulting in an induced autoimmune response.”

• Also stated in: § Neurodegenerative diseases · plain

  “Therefore, up-regulated miR-128-3p mediated the Th2 into Th1 cytokine shift by suppressing the development and activation of Th2 cells in patients with MS.69,70”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [69] Guerau-de-Arellano, 2011, Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity, Brain source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [70] Severin, 2016, MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis, Brain source

In the paper

“and stratified the samples into two clusters with the power of outcome prediction”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [45] Bronisz, 2020, The nuclear DICER-circular RNA complex drives the deregulation of the glioblastoma cell microRNAome, Sci. Adv. source

In the paper

“cooperative binding (microRNAs form complexes and jointly bind to mRNA targets, leading to enhanced or synergistic regulatory effects155)”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [155] Rinck, 2013, The human transcriptome is enriched for miRNA-binding sites located in cooperativity-permitting distance, RNA Biol. source

In the paper

“MiR-128-3p was identified as a target of several lncRNAs, and their direct interactions regulated neurogenesis and affected both CNS and tumor cells.”

What the sources say

• ?Not checked — no full text of the sourcecites [166] Geng, 2020, Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma, Eur. Rev. Med. Pharmacol. Sci. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [169] Fu, 2018, LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway, Neurotherapeutics source
• ?Not checked — no full text of the sourcecites [170] Dahai, 2020, Lowly expressed lncRNA PVT1 suppresses proliferation and advances apoptosis of glioma cells through up-regulating microRNA-128-1-5p and inhibiting PTBP1, Brain Res. Bull. source

In the paper

“The potential for off-target effects adds complexity to miR-128-3p therapeutic use (as is the case for any other microRNA), as microRNA-mediated targeting of a specific gene may unintentionally affect other players with adverse, unintended consequences.”

In the paper

“The interaction between lncRNA NEAT1 (Nuclear paraspeckle assembly transcript 1) and miR-128-3p that resulted in the sponging of this microRNA contributed not only to glioma pathogenesis,172 but also to the progression of spinal cord injury-mediated NPP.173”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [172] Chen, 2021, LncRNA NEAT1 Enhances Glioma Progression via Regulating the miR-128-3p/ITGA5 Axis, Mol. Neurobiol. source
• ?Not checked — no full text of the sourcecites [173] Xian, 2021, LncRNA NEAT1/miR-128-3p/AQP4 axis regulating spinal cord injury-induced neuropathic pain progression, J. Neuroimmunol. source

In the paper

“LncRNAs function as competing endogenous RNA (ceRNA) of specific microRNAs and, therefore, modulate the expression of downstream target mRNAs.166”

What the sources say

• ?Not checked — no full text of the sourcecites [166] Geng, 2020, Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma, Eur. Rev. Med. Pharmacol. Sci. source

In the paper

“as the knockdown of lncRNA HCP5 inhibited cell proliferation and enhanced radiosensitivity in gliomas.171”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [171] Wang, 2021, Knockdown of Long Non-Coding RNA HCP5 Increases Radiosensitivity Through Cellular Senescence by Regulating microRNA-128 in Gliomas, Cancer Manag. Res. source

In the paper

“These include competitive binding (microRNAs compete for binding to the same mRNA targets, leading to differential regulation of gene expression154)”

What the sources say

• ?Not checked — no full text of the sourcecites [154] Giza, 2014, MicroRNAs and ceRNAs: therapeutic implications of RNA networks, Expert Opin. Biol. Ther. source

In the paper

“While EVs exhibit some tissue or cell tropism,213,214 their targeting specificity can be less precise than synthetic delivery vehicles.”

What the sources say

• Not checked yetcites [213] Wiklander, 2015, Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting, J. Extracell. Vesicles source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [214] Batrakova, 2015, Using exosomes, naturally-equipped nanocarriers, for drug delivery, J. Control. Release source

In the paper

“Moreover, microRNAs can re-arrange a genetic and molecular landscape in a cell-type-specific manner130 due to the strict tissue and cell-type-specific distribution and functions of microRNAs,210 meaning their targets in cancer and normal cells are different.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [130] Rooj, 2017, MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells, Cell Rep. source
• Not checked yetcites [210] Sempere, 2004, Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation, Genome Biol. source

In the paper

“More importantly, EVs originating from non-malignant cells do not propagate pro-tumorigenic signals to cancer cells and are not toxic to normal cells and tissues.69,77,126,130,221”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [69] Guerau-de-Arellano, 2011, Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity, Brain source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [77] Peruzzi, 2013, MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells, Neuro Oncol. source
• ?Not checked — no full text of the sourcecites [126] Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal, Cancer Res. source

In the paper

“Although not based on EVs, they nevertheless highlight the ability of lipid vesicles to maintain the functionality of enclosed RNAs and effectively boost immune response in vivo.”

In the paper

“The opposite correlation of miR-128-3p expression—loss in malignant brain tumors and prominent up-regulation in neurodegeneration—clearly emphasizes the importance of its balanced expression, suggesting potential reverse therapeutic opportunities in both pathological states.”

In the paper

“The increasing interest in miR-128-3p and its interference with other ncRNAs and several signaling pathways suggests the high clinical relevance of miR-128-3p and makes it a good candidate for therapeutic intervention.”

In the paper

“Some functional studies provided several targets of miR-128-3p in cancer and immune cells,126,130 thus supporting the rationale for its application to enhance antitumor and pro-immune activity.”

What the sources say

• ?Not checked — no full text of the sourcecites [126] Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal, Cancer Res. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [130] Rooj, 2017, MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells, Cell Rep. source

In the paper

“However, the immunosuppressive character of glioblastoma manifested by a “cold” microenvironment that results in poor immune cell infiltration,180,181 concurrent with the fast progression of the disease, contributes to a short window for treatment opportunities.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [180] Reardon, 2016, Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model, Cancer Immunol. Res. source
• ?Not checked — no full text of the sourcecites [181] Caccese, 2019, PD-1/PD-L1 immune-checkpoint inhibitors in glioblastoma: A concise review, Crit. Rev. Oncol. Hematol. source

In the paper

“Cell-type-specific delivery systems, such as nanoparticle encapsulation of microRNA mimics or inhibitors, would minimize off-target effects and improve therapeutic efficacy.”

In the paper

“The varying expression patterns of miR-128-3p in different neurological disorders suggest that its function is context-dependent and influenced by various cellular and environmental factors.”

In the paper

“Moreover, EV-based delivery of microRNAs with proven anti-oncogenic and immune-enhancing properties, such as miR-128-3p, represents a potential experimental strategy for developing the therapy against glioblastoma and human cancer in general.”

In the paper

“The ability to prepare a large number of EVs carrying therapeutic microRNAs for cancer patients within a short time after surgery is also crucial, as the fast progression of the disease contributes to very limited opportunities for effective therapy.”

In the paper

“This observation led to the development of the following strategy: microRNAs lost in tumor cells, once reintroduced, are detrimental to them while not harming normal, healthy cells.”

In the paper

“These novel nucleic acid modifications play a crucial role in enhancing the efficacy of microRNAs in molecular therapy strategies for CNS diseases.”

In the paper

“Due to its high expression in neurodegenerative scenarios, miR-128-3p may be genetically or pharmacologically targeted to induce immunosuppression, as opposed to immune-boosting strategies, due to its dramatically reduced level in malignant brain tumors compared with normal brain tissue.”

In the paper

“Up-regulated expression of miR-128-3p within the CNS implicates its critical role in developing and maintaining the brain’s biological and physiological functions.”

In the paper

“In CNS disorders like AD, miR-128-3p inhibitors may be versatile, targeting PPARG and potentially reducing amyloid beta levels.53”

What the sources say

• ?Not checked — no full text of the sourcecites [53] Liu, 2019, MicroRNA-128 knockout inhibits the development of Alzheimer’s disease by targeting PPARγ in mouse models, Eur. J. Pharmacol. source

In the paper

“Conversely, replacing miR-128-3p would be effective for immune-boosting strategies in glioblastoma and, therefore, beneficial for patients.”

In the paper

“Incorporating targeting ligands, peptides, or aptamers is a promising strategy to improve EVs' targeting efficacy for therapeutic applications.”

In the paper

“MicroRNA-based strategies have gained attention as effective methods for sensitizing cancer cells because many microRNAs contribute to the increased resistance of cancer cells to standard treatments.206,207”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [206] Chen, 2021, Role of microRNAs in glioblastoma, Oncotarget source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [207] Mafi, 2022, Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment, Cell. Mol. Biol. Lett. source

In the paper

“The hypothesis is based on the observation that microRNAs often exhibit cell-type-specific functions and thus can regulate diverse biological processes in healthy and pathological tissue.”

In the paper

“This is due to their advantageous features, such as small size, the ability to enclose numerous molecules and particles, and the scaled-up production of specific engineered RNA-based agents.”

In the paper

“High levels of miR-28 in some neurodegenerative disorders open avenues for genetic or pharmacologic targeting to induce immunosuppression.”

In the paper

“This method has shown promising results, with a dataset of 1,370 effective drug-like compounds providing a valuable resource for further microRNA-based drug discovery.205”

What the sources say

• Not checked yetcites [205] Nguyen, 2023, Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing, Nat. Commun. source