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Cited by 190Cancer-related molecular mechanisms researchMicroRNA in disease regulationNeuroinflammation and Neurodegeneration Mechanisms

Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway

Open access
Yan, Honglin, Rao, Jie, Yuan, Jingping, Gao, Likun, Huang, Wenxian, Zhao, Lina, Ren, Jiacai·2017·Cell Death & Disease
DOI 10.1038/s41419-017-0047-yPMC PMC5870589
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Abstract

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been demonstrated as an important regulator in diverse human cancers. However, its function and regulatory mechanism in ischemic stroke remains largely unknown. Here, we report that MEG3 is physically associated with microRNA-21 (miR-21), while miR-21 is downregulated following ischemia in the ischemic core in vitro and in vivo, which is opposite to MEG3. Besides, overexpression of miR-21 protects oxygen–glucose deprivation and reoxygenation (OGD/R)-induced apoptotic cell death. Furthermore, MEG3 functions as a competing endogenous RNAs (ceRNAs) and competes with programmed cell death 4 (PDCD4) mRNA for directly binding to miR-21, which mediates ischemic neuronal death. Knockdown of MEG3 protects against ischemic damage and improves overall neurological functions in vivo. Thus, our data uncovers a novel mechanism of lncRNA MEG3 as a ceRNA by targeting miR-21/PDCD4 signaling pathway in regulating ischemic neuronal death, which may help develop new strategies for the therapeutic interventions in cerebral ischemic stroke.

AI snapshot

Written from the paper’s full text.

TL;DR

Long non-coding RNA MEG3 acts as a competing endogenous RNA for miR-21, preventing miR-21 from repressing PDCD4 and thereby promoting ischemic neuronal death. Knockdown of MEG3 protects against ischemia/reperfusion injury and improves neurological function in mice.

Key findings

  • MEG3 is physically associated with miR-21 via predicted binding sites; luciferase reporters with all three miR-21-binding sites mutated did not respond to increasing miR-21, whereas wild-type MEG3 reporters did.
  • miR-21 was downregulated after ischemia in vitro and in vivo, opposite to MEG3; miR-21 overexpression increased miR-21 expression ~3-fold, while miR-21 inhibitor reduced it to ~40%, and miR-21 overexpression reduced OGD/R-induced TUNEL-positive apoptotic cell death.
  • MEG3 competes with PDCD4 mRNA for binding to miR-21: miR-21 decreased PDCD4 mRNA/protein, but this effect was abolished by MEG3 overexpression and augmented by si-MEG3; MEG3 overexpression also abolished miR-21’s protection against OGD/R-induced neuronal death.
  • In vivo, si-MEG3 injection reduced I/R-induced brain infarct volume and neuronal death and improved neurological score, rotarod performance, Morris water maze learning/memory, and open-field locomotor/anxiety-like behavior compared with si-s-MEG3.

Methods

  • In vitro: N2a cells subjected to oxygen–glucose deprivation (3 h) followed by reoxygenation for 24, 48, or 72 h; transfection with miR-21 mimic/inhibitor, MEG3-expressing plasmids, si-MEG3, or controls.
  • In vivo: adult male C57BL/6 J mice underwent 60-min middle cerebral artery occlusion followed by reperfusion for 24, 48, or 72 h; si-MEG3 or si-s-MEG3 was injected into the lateral ventricle before MCAO.
  • Main assays: luciferase reporter assays, MS2-MBP RNA pulldown, qRT-PCR, western blot, TUNEL, TTC staining, Fluoro-Jade C staining, neurological deficit scoring, rotarod, Morris water maze, and open-field tests; statistics used GraphPad Prism with Student’s t-test and P < 0.05 significance.

Limitations

  • The paper states that it did not exclude other targets of MEG3 or miR-21 that may contribute to ischemic neuronal death, and notes that PDCD4 is not the only miR-21 target and miR-21 is not the only MEG3 target.
  • The paper states that whether MEG3/miR-21 targets crosstalk with the previously reported MEG3–p53 pathway remains to be analyzed in future studies.
  • Evident from the text: the study relies on N2a cells and male C57BL/6 J mice, with no human tissue or clinical validation reported.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41419-017-0047-y

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

16 of 22 cited sources checked · 10 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    lncRNAs act as competing endogenous RNAs (ceRNAs) by competing for binding to miRNAs.

    “increasing experimental evidence has confirmed that lncRNAs act as competing endogenous RNAs (ceRNAs) by competing for binding to miRNAs”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [16] Cesana, M. et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147, 358–369 (2011). source
    • cites [17] Liu, X. et al. The mechanism of long non-coding RNA MEG3 for neurons apoptosis caused by hypoxia: mediated by miR-181b-12/15-LOX signaling pathway. Front. Cell. Neurosci. 10, 201 (2016). source
    • cites [18] Tay, Y., Rinn, J. & Pandolfi, P. P. The multilayered complexity of ceRNA crosstalk and competition. Nature 505, 344–352 (2014). source
  • Premisecitation

    miR-21 protects spinal cords against ischemia-reperfusion injury by inhibiting PDCD4.

    “Additionally, miRNA-21 protects spinal cords against ischemia-reperfusion injury by inhibition of PDCD438.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] He, F. et al. Overexpression of microRNA-21 protects spinal cords against transient ischemia. J. Thorac. Cardiovasc. Surg. 152, 1602–1608 (2016). source
  • Premisecitation

    LncRNAs can share common miRNA binding sites of mRNAs, thereby blocking the binding of target mRNAs to miRNAs and abolishing the downstream effects of those miRNAs.

    “Moreover, lncRNAs could share common miRNA binding sites of mRNAs, thus blocking the binding of target mRNAs to miRNAs and abolishing the downstream effects of these miRNAs25.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [25] Salmena, L., Poliseno, L., Tay, Y., Kats, L. & Pandolfi, P. P. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146, 353–358 (2011). source

      The ceRNA hypothesis sections describe non-coding RNAs competing with mRNAs for shared microRNA binding and give an example of an lncRNA sequestering a microRNA (page numbers unavailable). They describe impaired microRNA activity and diluted repression, not complete blocking of microRNA binding to target mRNAs or abolition of its downstream effects. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    In ischemia, miR-21 has been shown to be a strong anti-apoptosis and pro-survival factor that can downregulate the expression of apoptosis-related proteins.

    “As for ischemia, miR-21 has been shown to be a strong anti-apoptosis and pro-survival factor, which could downregulate the expression of apoptosis related proteins32,33.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [32] Han, Z. et al. miR-21 alleviated apoptosis of cortical neurons through promoting PTEN-Akt signaling pathway in vitro after experimental traumatic brain injury. Brain Res. 1582, 12–20 (2014). source
    • cites [33] Buller, B. et al. MicroRNA-21 protects neurons from ischemic death. FEBS J. 277, 4299–4307 (2010). source
  • Premisecitation

    The miR-21/PDCD4 pathway exerts anti-apoptotic effects against cell death in various diseases.

    “Existing evidence revealed that miR-21/PDCD4 pathway exerts anti-apoptotic effects against cell death in various diseases36.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [36] Xiao, J. et al. Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death Dis. 7, e2277 (2016). source

      The Results section reports that miR-21 reduced oxidative-stress-induced apoptosis in H9C2 cardiomyocytes by targeting PDCD4. The paper does not establish that this anti-apoptotic effect occurs across various diseases; its direct evidence is limited to the studied cardiac-cell model. Page numbers are not available in the supplied passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 9
  • May combine two claims. 14

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    MEG3 is an imprinted gene located on chromosome 14q32.3 in humans and functions as a lncRNA.

    “Maternally expressed gene 3 (MEG3), also known as gene trap locus 2 (Gtl2), is an imprinted gene located on chromosome 14q32.3 in humans and functions as a lncRNA19.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [19] Zhang, X. et al. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endocrinology 151, 939–947 (2010). source

      The Abstract identifies human MEG3 as an imprinted gene that encodes a noncoding RNA, supporting its description as a lncRNA. Our copy does not state that MEG3 is located at human chromosome 14q32.3; a reference title mentions a 14q32.2 imprinted region but does not establish the claimed location. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    miRNAs are critical mediators of ischemia.

    “Among these RNAs, miRNAs are the most studied of all ncRNAs as critical mediator of ischemia4,5.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [4] Saugstad, J. A. Non-coding RNAs in stroke and neuroprotection. Front. Neurol. 6, 50 (2015). source
    • cites [5] Vemuganti, R. All’s well that transcribes well: non-coding RNAs and post-stroke brain damage. Neurochem. Int. 63, 438–449 (2013). source

  • Classified as probably not a substantial claim.

    Premisecitation

    miR-21 protects cardiomyocytes against H2O2-induced apoptosis by targeting PDCD4.

    “For example, miR-21 protects cardiomyocytes against H2O2 induced cell apoptosis by targeting the proapoptotic proteins PDCD437.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [37] Cheng, Y. et al. MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. J. Mol. Cell. Cardiol. 47, 5–14 (2009). source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miR-21 is widely expressed in mammalian cells, is located on chromosome 17q23.2 in humans, and its upregulation is associated with various types of solid tumors.

    “miR-21 is a widespread expression of miRNA in mammalian cells located on chromosome 17q23.2 in humans, whose upregulation is associated with various types of solid tumors29–31.”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [29] Baez-Vega, P. M. et al. Targeting miR-21-3p inhibits proliferation and invasion of ovarian cancer cells. Oncotarget 7, 36321–36337 (2016). source

      The Introduction (page unavailable) says miR-21-5p is overexpressed in most cancers, supporting the tumor-association part of the claim. It does not establish that miR-21 is widely expressed in mammalian cells or locate the human gene at chromosome 17q23.2; searches for those details found no supporting passage. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [30] Moore, L. M. & Zhang, W. Targeting miR-21 in glioma: a small RNA with big potential. Expert Opin. Ther. Targets 14, 1247–1257 (2010). source
    • cites [31] Krichevsky, A. M. & Gabriely, G. miR-21: a small multi-faceted RNA. J. Cell. Mol. Med. 13, 39–53 (2009). source

      The section on mechanisms of miR-21 elevation maps the human gene to chromosome 17q23.2, and the section on expression in cancer reports upregulation across several types of solid tumour. The paper says miR-21 is conserved in mammals, but the passages do not establish that it is widely expressed in mammalian cells; conservation is not the same as widespread expression. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    ceRNAs, such as lncRNAs, compete for binding to miRNAs through miRNA response elements (MREs), preventing miRNA binding to target mRNAs.

    “ceRNAs, such as lncRNAs, could compete for binding to miRNAs through miRNA response elements (MREs), thus preventing the binding of miRNAs to target mRNAs25.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [25] Salmena, L., Poliseno, L., Tay, Y., Kats, L. & Pandolfi, P. P. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146, 353–358 (2011). source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MEG3 serves as a ceRNA for miR-21 to regulate cell proliferation or apoptosis in some tumors.

    “More significantly, studies have revealed that MEG3 serves as a ceRNA for miR-21 to regulate cell proliferation or apoptosisin in some tumors34,35, but whether MEG3 competes with mRNA for miR-21 in ischemia and contributes to ischemic neuronal death remained unexplored.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [34] Zhang, J. et al. Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21. Cancer Biol. Ther. 17, 104–113 (2016). source

      The Results and Discussion (page not provided) report that MEG3 regulates miR-21-5p and affects proliferation and apoptosis in cervical cancer cells. They do not establish that MEG3 acts as a competing endogenous RNA (ceRNA) for miR-21; the Discussion says the exact mechanism of their interaction requires further study. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [35] Zhou, X., Yuan, P., Liu, Q. & Liu, Z. LncRNA MEG3 regulates imatinib resistance in chronic myeloid leukemia via suppressing MicroRNA-21. Biomol. Therap. 25, 490–496 (2017). source

  • May combine two claims.

    Findingown data

    MEG3 overexpression abolishes the protective effect of miR-21 on OGD/R-induced neuronal death, while si-MEG3 augments it.

    “the protection effect of miR-21 on OGD/R-induced neuronal death were abolished by MEG3 overexpression, and augmented by si-MEG3”
    • Also stated in: § MEG3 contradicts the inhibitory effects of miR-21 on PDCD4 to regulate ischemic neuronal death · plain
      “more TUNEL-positive cells when cotransfection of miR-21 mimic + MEG3-expressing plasmid, while less TUNEL-positive cells when cotransfection of miR-21 mimic + si-MEG3”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The N2a cell OGD/R model is a valid model of ischemic neuronal death in vivo.

  • May combine two claims.

    Findingown data

    In the open-field test 3 days after MCAO, mice treated with si-MEG3 showed higher average velocity and spent more time in the center area of the apparatus than mice treated with si-s-MEG3.

    “In this assessment, mice treated with si-MEG3 showed a higher velocity and spent more time in the center area of the apparatus than mice treated with si-s-MEG3, indicating an improved locomotor activity and anxiety-like behavior (Fig. 7e).”
    • Also stated in: § Knockdown of MEG3 protects against ischemic damage and improves neurological deficits in vivo · plain
      “Open-field test. The performance on open-field test of three groups (sham-treated mice, si-s-MEG3 and si-MEG3 injection mice subjected to MCAO operation) was analyzed 3 days after MCAO operation. Data represent means ± S.E.M. for 12 mice per group. * P < 0.05 by Student’s t-test”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Bioinformatics analysis identified that MEG3 targets miR-21 and might play an important role in ischemic neuronal death.

    “With bioinformatics, we identified that the cell death promoter MEG3 target miR-21 and hence might play an important role in ischemic neuronal death.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Knockdown of MEG3 improves neurological function, motor coordination, and spatial learning/memory after MCAO in mice.

    “better neurological score in si-MEG3 injection mice compared with si-s-MEG3”
    • Also stated in: § Knockdown of MEG3 protects against ischemic damage and improves neurological deficits in vivo · plain
      “si-MEG3 injection resulted in better recovery of motor coordination in rotarod test”
    • Also stated in: § Knockdown of MEG3 protects against ischemic damage and improves neurological deficits in vivo · plain
      “Long-term learning and memory deficits were significantly improved in si-MEG3 treatment mice after MCAO”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The MCAO mouse model is a valid model of human ischemic stroke.

  • May combine two claims.

    Findingown data

    The authors' results supported that the miR-21/PDCD4 pathway exerts anti-apoptotic effects, and further confirmed that the miR-21/PDCD4 pathway is regulated by MEG3.

    “Our results also supported this fact, moreover, we further confirmed that miR-21/PDCD4 pathway were regulated by MEG3.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MEG3 overexpression abolishes the inhibitory effect of miR-21 on PDCD4 expression, while si-MEG3 augments it.

    “the effects of miR-21 on PDCD4 were abolished by MEG3 overexpression, and augmented by si-MEG3”
    • Also stated in: § MEG3 competes with PDCD4 mRNA for binding to miR-21 · hedged
      “the suppressive effects of miR-21 on the luciferase activity of pmirGLO-PDCD4-WT could be abolished by overexpression of MEG3, while augmented by si-MEG3”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    si-MEG3 treatment markedly improved long-term learning and memory deficits, locomotor activity and anxiety-like behavior post-ischemia.

    “And what’s more, si-MEG3 treatment markedly improved long-term learning and memory deficits, locomotor activity and anxiety-like behavior post-ischemia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    si-MEG3 injection revealed a better neurological score and recovery of motor coordination in mice after I/R.

    “On the other hand, si-MEG3 injection revealed a better neurological score and recovery of motor coordination in mice after I/R.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In the present study, MEG3 affects PDCD4 expression through downregulation of miR-21 and counteracts the inhibitory effect of miR-21 on PDCD4, abolishing miR-21's protection in ischemic neuronal death.

    “In the present study, MEG3 affects PDCD4 expression through downregulation of the miR-21 level and contradicts the inhibitory effects of miR-21 on PDCD4 to abolish the protection effect of miR-21 in ischemic neuronal death.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Knockdown of MEG3 improves locomotor activity and anxiety-like behavior in mice after MCAO.

    “indicating an improved locomotor activity and anxiety-like behavior (Fig. 7e).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the authors' previous study, they determined the expression and function of lncRNA MEG3 in cerebral ischemia.

    “In our previous study, we first determined the expression and function of lncRNA MEG3 in cerebral ischemia24.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Yan, H., Yuan, J., Gao, L., Rao, J. & Hu, J. Long noncoding RNA MEG3 activation of p53 mediates ischemic neuronal death in stroke. Neuroscience 337, 191–199 (2016). source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The study did not exclude the possibility that other targets of MEG3 or miR-21 may also contribute to ischemic neuronal death.

    “Although here we described that MEG3 competed with PDCD4 mRNA for binding to miR-21 in ischemia, we didn’t exclude the possibility of other targets of MEG3 or miR-21 which may also contribute to the ischemic neuronal death.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: PDCD4 is not the only target of miR-21, and miR-21 is not the only target of MEG3.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premiseown data

    The authors previously confirmed that MEG3 activated p53-mediated transactivation to mediate neuronal death in cerebral ischemia.

    “Besides, we previously confirmed that MEG3 activated p53-mediated transactivation to mediate neuronal death in cerebral ischemia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Knockdown of MEG3 protects against ischemic damage and neurological deficits.

    “Thus, knockdown of MEG3 protects against ischemic damage and neurological deficits.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Knockdown of MEG3 enhances the protection effects of the miR-21/PDCD4 pathway and prevents subsequent ischemic brain injury.

    “Knockdown of MEG3 enhanced the protection effects of miR-21/PDCD4 pathway and prevents the followed ischemic brain injury.”
    Quote in the paperSubstantial claim
21 of 21

  • The paper relies on this without support.

    PDCD4 is the downstream effector through which miR-21 and MEG3 regulate ischemic neuronal death.

    “These series of results indicated that MEG3 regulates ischemic neuronal death by contradicting the inhibitory effects of miR-21 on PDCD4.”

  • The paper relies on this without support.

    The N2a cell OGD/R model is a valid model of ischemic neuronal death in vivo.

    “Then, N2a cell oxygen–glucose deprivation and reoxygenation (OGD/R) model was established to further determine the expression of miR-21 in response to ischemia in vitro”

  • The paper relies on this without support.

    The MCAO mouse model is a valid model of human ischemic stroke.

    “focal cerebral ischemia was induced in adult male mice by middle cerebral artery occlusion (MCAO) for 60 min”

  • The paper relies on this without support.

    MEG3 has not been functionally characterized in ischemia, so the mechanisms underlying its effects in ischemia need deeper exploration.

    “However, although the relationship of MEG3 expression with a variety of tumors has been confirmed20–23, MEG3 have not been functionally characterized in ischemia, thus, the mechanisms underlying the effects of MEG3 in ischemia still needs to be explored deeply.”

  • The paper relies on this without support.

    PDCD4 is not the only target of miR-21, and miR-21 is not the only target of MEG3.

    “Since PDCD4 is not the only target of miR-21, similarly, miR-21 is not the only target of MEG3, some other targets of MEG3/miR-21 should be further analysed in the further experiments.”
5 of 5

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.

  • MEG3 is described as both previously characterized and uncharacterized in ischemia

    Minor

    The discussion says the authors previously determined MEG3's function in cerebral ischemia, then says it had not been functionally characterized in ischemia.

  • Mutant MEG3 is reported to enrich miR-21 despite losing its miR-21 reporter response

    Minor

    The luciferase assay reports no response to increasing miR-21 after all three predicted binding sites are mutated. The pulldown result instead reports miR-21 enrichment for MEG3 bearing mutations in those same three sites, conflicting with the paper's interpretation that these sites account for the observed association.

2 of 2

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Related

Authors
Yan, H., Rao, J., Yuan, J., Gao, L., Huang, W., Zhao, L., & Ren, J.
Affiliations
Renmin Hospital of Wuhan University (CN)
Corresponding author
Yuan, Jingping
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2017-12-13
Volume
8
Issue
12
Pages
3211-3211
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-017-0047-y
PMC
PMC5870589
OpenAlex
W2774335059
Semantic Scholar
1d0de784b8f56e5e7612c00346d903c2912ff552
Cited by
190
References
38
Citations by year
2026: 6 · 2025: 11 · 2024: 6 · 2023: 13 · 2022: 26 · 2021: 41 · 2020: 32 · 2019: 31 · 2018: 22
FWCI
6.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (31600866)
  • Wuhan University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
MEG3, long non-coding RNA, competing endogenous RNA, miR-21, PDCD4, ischemic stroke, cerebral ischemia, neuronal apoptosis, oxygen-glucose deprivation/reoxygenation, microRNA sponge, neurological function
MeSH terms
Animals, Base Sequence, Binding, Competitive, Cell Line, Brain Ischemia, Disease Models, Animal, Gene Expression Regulation, Glucose, Humans, Male, Mice, Inbred C57BL, Neurons, RNA, Messenger, Signal Transduction, Cell Hypoxia, RNA-Binding Proteins, Apoptosis, Maze Learning, Base Pairing, Stroke, MicroRNAs, Apoptosis Regulatory Proteins, Mice, RNA, Long Noncoding

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