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Cited by 242MicroRNA in disease regulationNeuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke Management

MicroRNA‐21 protects neurons from ischemic death

Open access
Buller, Ben, Liu, Xianshuang, Wang, Xinli, Zhang, Rui L., Zhang, Li, Hozeska‐Solgot, Ann, Chopp, Michael, Zhang, Zheng G.·2010·The FEBS Journal
DOI 10.1111/j.1742-4658.2010.07818.xPMC PMC2957309
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Abstract

MicroRNAs are small RNAs that attenuate protein expression by complementary binding to the 3′‐UTR of a target mRNA. Currently, very little is known about microRNAs after cerebral ischemia. In particular, microRNA‐21 (miR‐21) is a strong antiapoptotic factor in some biological systems. We investigated the role of miR‐21 after stroke in the rat. We employed in situ hybridization and laser capture microdissection in combination with real‐time RT‐PCR to investigate the expression of miR‐21 after stroke. In situ hybridization revealed that miR‐21 expression was upregulated in neurons of the ischemic boundary zone, and quantitative real‐time RT‐PCR analysis revealed that stroke increased mature miR‐21 levels by approximately threefold in neurons isolated from the ischemic boundary zone by laser capture microdissection as compared with homologous contralateral neurons 2 days (n = 4; P < 0.05) and 7 days (n = 3; P < 0.05) after stroke. In vitro, overexpression of miR‐21 in cultured cortical neurons substantially suppressed oxygen and glucose deprivation‐induced apoptotic cell death, whereas attenuation of endogenous miR‐21 by antisense inhibition exacerbated cell death after oxygen and glucose deprivation. Moreover, overexpression of miR‐21 in neurons significantly reduced FASLG levels, and introduction of an miR‐21 mimic into 293‐HEK cells substantially reduced luciferase activity in a reporter system containing the 3′‐UTR of Faslg. Our data indicate that overexpression of miR‐21 protects against ischemic neuronal death, and that downregulation of FASLG, a tumor necrosis factor‐α family member and an important cell death‐inducing ligand whose gene is targeted by miR‐21, probably mediates the neuroprotective effect. These novel findings suggest that miR‐21 may be an attractive therapeutic molecule for treatment of stroke.

AI snapshot

Written from the paper’s full text.

TL;DR

In rat stroke and cultured cortical neurons, miR-21 is upregulated in ischemic boundary zone neurons and protects against oxygen-glucose deprivation-induced apoptosis, at least partly by targeting the Faslg 3′UTR and reducing FASLG protein.

Key findings

  • Stroke increased mature miR-21 in laser-captured IBZ neurons by 3.5 ± 1.8 fold at 2 days (n=4; P<0.05) and 3.2 ± 0.5 fold at 7 days (n=3; P<0.05) versus contralateral neurons; miR-9 and miR-335 showed no significant changes (n=3; P>0.2).
  • In cultured cortical neurons after OGD, miR-21 overexpression reduced dead cells to 24.6 ± 4.7% versus 31.7 ± 4.9% for miR-67 control, while antisense inhibition increased death to 42.2 ± 6.8% (n=5; P<0.05, ANOVA). TUNEL positivity was 9.9 ± 7.7% with miR-21 overexpression versus 37.8 ± 15.8% with miR-21 inhibition (n=10; P<0.05, ANOVA).
  • OGD induced FASLG protein 1.37 ± 0.23 fold (n=3; P<0.05); miR-21 overexpression knocked down FASLG protein by 32 ± 11% (n=4; P<0.05) without significantly changing Faslg mRNA (1.17 ± 0.34; n=3; P>0.4).
  • A Faslg 3′UTR luciferase reporter was attenuated by 43 ± 13% with miR-21 mimic versus miR-67 (n=4; P<0.02); mutation of the putative 9-mer binding site abolished the effect.

Methods

  • Male Wistar rats (350–450 g) underwent embolic middle cerebral artery occlusion; brains were analyzed by in situ hybridization, immunofluorescence, laser capture microdissection of NeuN-positive IBZ and contralateral neurons, and real-time RT-PCR.
  • Primary rat embryonic day 17 cortical neurons were subjected to 3 h oxygen-glucose deprivation followed by 24 h recovery; neurons were transfected with miR-21 mimic, miR-21 inhibitor, or miR-67 control and assessed by live/dead assay, TUNEL, and Western blot.
  • Target prediction used PicTar, TargetScan 5.1, and miRanda; luciferase reporter assays were performed in 293-HEK cells. Statistics used one-way ANOVA and two-sample t-tests with P<0.05 considered significant.

Limitations

  • The paper states the data are preliminary and that further investigation of miR-21 modulation on neuronal cell death in vivo is warranted.
  • Evident from the text: in vitro OGD did not significantly change miR-21 expression (0.63 ± 0.24 at 2 days, n=3, P>0.1; 0.78 ± 0.47 at 7 days, n=3, P>0.5), possibly because the cultured neurons were immature or lacked glial factors; functional protection was shown in vitro, not in an in vivo stroke outcome model.
  • Evident from the text: several experiments used small sample sizes (n=3–5 in some assays), and the live/dead assay difference was described as statistically insignificant, attributed to background necrosis.

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

Integrity signals

Registry

Crossref · 10.1111/j.1742-4658.2010.07818.x

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 28 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    miR-21 has been shown to be a strong antiapoptotic factor.

    “In particular, miRNA-21 (miR-21) has been shown to be a strong antiapoptotic factor [5, 9–11].”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [5] Chan JA Krichevsky AM Kosik KS 2005 MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells Cancer Res 65 6029 6033 65/14/6029 [pii] 10.1158/0008-5472.CAN-05-0137 16024602 source
    • cites [9] Chen Y Liu W Chao T Zhang Y Yan X Gong Y Qiang B Yuan J Sun M Peng X 2008 MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G Cancer Lett 272 197 205 S0304-3835(08)00526-0 [pii] 10.1016/j.canlet.2008.06.034 19013014 source
    • cites [10] Frankel LB Christoffersen NR Jacobsen A Lindow M Krogh A Lund AH 2008 Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells J Biol Chem 283 1026 1033 M707224200 [pii] 10.1074/jbc.M707224200 17991735 source
    • cites [11] Papagiannakopoulos T Shapiro A Kosik KS 2008 MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells Cancer Res 68 8164 8172 68/19/8164 [pii] 10.1158/0008-5472.CAN-08-1305 18829576 source
  • Premisecitation

    miR-21 functions at least in part by targeting a host of pro-apoptotic genes.

    “miR-21 functions–at least in part–by targeting a host of pro-apoptotic genes [13, 14].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [13] Kim YJ Hwang SJ Bae YC Jung JS 2009 MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue Stem Cells 27 3093 3102 10.1002/stem.235 19816956 source
    • cites [14] Meng F Henson R Wehbe-Janek H Ghoshal K Jacob ST Patel T 2007 MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer Gastroenterology 133 647 658 S0016-5085(07)01002-5 [pii] 10.1053/j.gastro.2007.05.022 17681183 PMC4285346 source

      The Results identify PTEN as a direct target of miR-21, and the Discussion reports anti-apoptotic effects of miR-21 in other cancers. But this paper does not show that miR-21 targets a host of pro-apoptotic genes; it identifies one direct target and only speculates about others. Page numbers were not provided in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Findingown data

    Co-transfection of miR-21 antisense inhibitor with miR-21 and Faslg-luc recovers luciferase activity to near control levels (2 ± 4% difference).

    “when miR-21 and a miR-21 antisense inhibitor were simultaneously cotransfected with Faslg-luc plasmid, the attenuation completely recovered, showing only a 2 ± 4% difference from the control (n=4; P<0.8; Fig. 3C).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The miR-21 binding site in the Faslg 3′UTR characterized in 293T-HEK cells is functional in neurons.
  • Findingown data

    Stroke increases mature miR-21 levels by approximately 3-fold in neurons isolated from the IBZ by LCM compared to homologous contralateral neurons at 2 and 7 days after stroke.

    “quantitative real-time RT-PCR analysis revealed that stroke increased mature miR-21 levels by ~3 fold in neurons isolated from the IBZ by LCM compared to homologous contralateral neurons 2 (n=4; P<0.05) and 7(n=3; P<0.05) days after stroke.”
    • Also stated in: § miR-21 is expressed in neurons in the IBZ · plain
      “At 2 days post-MCAo, we found that there is a notable upregulation of miR-21 in ipsilateral neurons compared to those in the homologous region of the contralateral hemisphere, with an average induction of 3.5 ± 1.8 fold (n=4; P<0.05), when normalized to U6 snRNA. At 7d after stroke miR-21 expression remained robust, with an average induction of 3.2 ± 0.5 times contralateral expression (n=3; P<0.05”
    Quote in the paperSubstantial claim
  • Findingown data

    Mutation of the 9-mer putative miR-21 binding site in the Faslg 3′UTR abolishes the difference in luciferase activity between experimental groups.

    “After transfection with Mut-luc, there was no statistically significant difference in any experimental group (Fig. 3C), indicating that the 9-mer portion of Faslg that is complementary to miR-21 is necessary for translational inhibition.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The miR-21 binding site in the Faslg 3′UTR characterized in 293T-HEK cells is functional in neurons.
  • Classified as probably not a substantial claim. 12
  • May combine two claims. 9

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

    Premisecitation

    miRNAs inhibit translation of mRNAs by guiding RISC to the mRNA via complementarity to its 3′UTR, thereby limiting a gene's functionality even though transcription may not be stopped.

    “miRNAs inhibit translation of mRNAs by guiding an inhibitory protein complex, the RNA induced silencing complex (RISC) to the mRNA via complementarity to its 3′ untranslated region (3′UTR), thereby limiting a gene’s functionality, even though transcription of the gene may not be stopped [4].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Pillai RS 2005 MicroRNA function: multiple mechanisms for a tiny RNA? RNA 11 1753 1761 11/12/1753 [pii] 10.1261/rna.2248605 16314451 PMC1370863 source

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

    Premisecitation

    miR-21 is upregulated in most solid tumors, including breast, colorectal and glioma.

    “It is upregulated in most solid tumors, including breast, colo-rectal and glioma [5, 10, 12].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [5] Chan JA Krichevsky AM Kosik KS 2005 MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells Cancer Res 65 6029 6033 65/14/6029 [pii] 10.1158/0008-5472.CAN-05-0137 16024602 source
    • cites [10] Frankel LB Christoffersen NR Jacobsen A Lindow M Krogh A Lund AH 2008 Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells J Biol Chem 283 1026 1033 M707224200 [pii] 10.1074/jbc.M707224200 17991735 source
    • cites [12] Zhang Z Li Z Gao C Chen P Chen J Liu W Xiao S Lu H 2008 miR-21 plays a pivotal role in gastric cancer pathogenesis and progression Lab Invest 88 1358 1366 labinvest200894 [pii] 10.1038/labinvest.2008.94 18794849 source

      The Abstract reports miR-21 overexpression in diverse solid tumors and specifically describes elevated expression in breast tumors and glioblastoma. It does not establish upregulation in most solid tumors, and its mention of colon cancer concerns aberrant miRNA expression generally, not miR-21 specifically. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Cardiac fibroblasts increase miR-21 expression specifically in the injured region after myocardial infarction, and this increase serves a protective role.

    “cardiac fibroblasts have been shown to increase miR-21 expression specifically in the injured region after myocardial infarction, and that this increase serves a protective role [30].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [30] Dong S Cheng Y Yang J Li J Liu X Wang X Wang D Krall TJ Delphin ES Zhang C 2009 MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction J Biol Chem 284 29514 29525 M109.027896 [pii] 10.1074/jbc.M109.027896 19706597 PMC2785585 source

      The Discussion (page unavailable) reports increased miR-21 in the border area after infarction and decreased expression in the infarcted area. The Abstract and Discussion report protective effects of miR-21, but the experiments identify cardiac myocytes, not fibroblasts; they do not show that fibroblasts specifically increase miR-21 in the injured region. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

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

    Premisecitation

    RNAi has been employed preclinically and clinically in treatment of several types of disease including viruses and cancer, but has not been employed in stroke therapy.

    “RNAi has been employed preclinically and clinically in treatment of several types of disease including viruses and cancer [26, 27], but has not been employed in stroke therapy.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [26] Huang DD 2008 The potential of RNA interference-based therapies for viral infections Curr HIV/AIDS Rep 5 33 39 18417033 PMC7088822 source
    • cites [27] Pirollo KF Chang EH 2008 Targeted delivery of small interfering RNA: approaching effective cancer therapies Cancer Res 68 1247 1250 68/5/1247 [pii] 10.1158/0008-5472.CAN-07-5810 18316585 source

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

    Premisecitation

    miR-21 is upregulated in response to H2O2 injury in cardiac myocytes and functions to attenuate apoptosis in that cell population.

    “Cheng et al. have shown that miR-21 is upregulated in response to H2O2 injury in cardiac myocytes, and that it functions to attenuate apoptosis in that cell population [29].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Cheng Y Liu X Zhang S Lin Y Yang J Zhang C 2009 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 S0022-2828(09)00017-0 [pii] 10.1016/j.yjmcc.2009.01.008 19336275 PMC3593965 source

  • May combine two claims.

    Findingown data

    Overexpression of miR-21 in cultured cortical neurons after OGD knocks down FASLG protein by 32 ± 11%, recovering it to levels observed in naïve neurons.

    “overexpression of miR-21 knocked down FASLG protein by 32 ± 11% (n=4; P<0.05; Fig. 3B), which completely recoved it to levels we observed in naïve neurons.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Transfection with miR-21 mimic increases functional miR-21 levels in cultured neurons.

  • May combine two claims.

    Findingown data

    miR-9 and miR-335 do not show significant changes in expression after MCAo at 2 or 7 days.

    “Neither miR-9 nor miR-335 showed significant changes at either timepoint, and neither were consistently up or downregulated after MCAo at either timepoint (n=3; P>0.2 for all genes/timepoints).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Ischemia-induced enhancement of FASLG expression recruits inflammatory cells to the infarcted area.

    “ischemia induced enhancement of FASLG expression recruits imflammatory cells to the infarcted area [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Rosenbaum DM Gupta G D’Amore J Singh M Weidenheim K Zhang H Kessler JA 2000 Fas (CD95/APO-1) plays a role in the pathophysiology of focal cerebral ischemia J Neurosci Res 61 686 692 10.1002/1097-4547(20000915) 61:6<686::AID-JNR12>3.0.CO;2-7 [pii] 10972965 source

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

    Premisecitation

    FASLG has been proposed as a therapeutic target for acute treatment of stroke.

    “FASLG has therefore been proposed as a therapeutic target for acute treatment of stroke [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] French LE Tschopp J 2003 Protein-based therapeutic approaches targeting death receptors Cell Death Differ 10 117 123 10.1038/sj.cdd.4401185 4401185 [pii] 12655300 source

  • May combine two claims.

    Premisecitation

    Neurons in the IBZ may be salvageable, and their viability has been correlated to positive functional outcomes.

    “Neurons in the IBZ may be salvageable, and the viability of these cells has been correlated to positive functional outcomes [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Lim SH Lee JS Lee JI Im S Ko YJ Kim HW 2008 The quantitative assessment of functional impairment and its correlation to infarct volume in rats with transient middle cerebral artery occlusion Brain Res 1230 303 309 S0006-8993(08)01655-7 [pii] 10.1016/j.brainres.2008.07.002 18675259 source

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

    Premisecitation

    TNFα signaling contributes to ischemic injury of neurons.

    “TNFα signaling is well known to contribute to ischemic injury of neurons [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Barone FC Arvin B White RF Miller A Webb CL Willette RN Lysko PG Feuerstein GZ 1997 Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury Stroke 28 1233 1244 9183357 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Cultured neurons derived from mice with mutant FASLG that cannot interact with FAS are more resistant to cell death from OGD.

    “Cultured neurons derived from mice with mutant FASLG that cannot interact with FAS, have been shown to be more resistant to cell death from OGD [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Martin-Villalba A Hahne M Kleber S Vogel J Falk W Schenkel J Krammer PH 2001 Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke Cell Death Differ 8 679 686 10.1038/sj.cdd.4400882 11464212 source

  • Classified as probably not a substantial claim.

    Premisecitation

    FASLG induces cell death by binding to its receptor FAS, leading to caspase-dependent apoptosis.

    “FASLG induces cell death by binding to its receptor, FAS, leading to caspase-dependant apoptosis [16, 17].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] Becher B Barker PA Owens T Antel JP 1998 CD95-CD95L: can the brain learn from the immune system? Trends Neurosci 21 114 117 S0166-2236(97)01180-6 [pii] 9530918 source
    • cites [17] Nagata S Golstein P 1995 The Fas death factor Science 267 1449 1456 7533326 source

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

    Premisecitation

    miR-21 is globally upregulated in response to traumatic brain injury (TBI).

    “Lei et al. have shown that miR-21 is globally upregulated in response to traumatic brain injury (TBI) [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Lei P Li Y Chen X Yang S Zhang J 2009 Microarray based analysis of microRNA expression in rat cerebral cortex after traumatic brain injury Brain Res 1284 191 201 S0006-8993(09)01094-4 [pii] 10.1016/j.brainres.2009.05.074 19501075 source

  • May combine two claims.

    Premisecitation

    tPA is the only drug available to stroke victims, with a limited window of about 4.5 hours from symptom onset.

    “Currently, only one drug, tissue plasminogen activator (tPA) is available to stroke victims, and it has a limited window of about 4.5 hours from the onset of symptoms in which it can be used for treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Fields JD Lindsay K Liu KC Nesbit GM Lutsep HL 2010 Mechanical thrombectomy for the treatment of acute ischemic stroke Expert Rev Cardiovasc Ther 8 581 592 10.1586/erc.10.8 20397831 source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Knockdown of Faslg by synthetic siRNA in ischemic kidney protects renal cells from apoptosis and whole animals from death.

    “Hamar et al. targeted Faslg by synthetic siRNA in ischemic kidney and showed that knockdown of Faslg protects renal cells from apoptosis, and, in fact, whole animals from death [28].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Hamar P Song E Kokeny G Chen A Ouyang N Lieberman J 2004 Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury Proc Natl Acad Sci U S A 101 14883 14888 0406421101 [pii] 10.1073/pnas.0406421101 15466709 PMC522049 source

  • May combine two claims.

    Premisecitation

    tPA is not safe for all patients, leading to only about 5% of stroke sufferers receiving tPA therapy.

    “Furthermore, it is not safe for all patients, leading to only about 5% of stroke sufferers actually receiving tPA therapy [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Fields JD Lindsay K Liu KC Nesbit GM Lutsep HL 2010 Mechanical thrombectomy for the treatment of acute ischemic stroke Expert Rev Cardiovasc Ther 8 581 592 10.1586/erc.10.8 20397831 source
17 of 17

  • The paper relies on this without support.

    The role of miR-21 in stroke has not been reported.

    “Specifically, its role in stroke has not been reported.”

  • The paper relies on this without support.

    The underlying molecular mechanisms that determine which neurons live or die after stroke are not entirely understood.

    “Currently, the underlying molecular mechanisms that determine which neurons live or die are not entirely understood.”

  • The paper relies on this without support.

    OGD in cultured cortical neurons is a valid model of ischemic neuronal death in vivo.

    “we employed a model of ischemia in which primary cortical neurons from rat embryos were subjected to oxygen and glucose deprivation (OGD).”

  • The paper relies on this without support.

    miR-67 is inert and not expressed in mammals.

    “cells transfected with miR-67, an inert, C. elegans-derived miRNA not expressed in mammal, were 31.7 ± 4.9% (average ± SD; n=5) dead.”
    “negative control miRNA mimic (based on cel-miR-67 sequence, which lacks homology in mammal; Dharmacon, Lafayette, CO)”

  • The paper relies on this without support.

    The miR-21 binding site in the Faslg 3′UTR characterized in 293T-HEK cells is functional in neurons.

    “When Faslg-luc was cotransfected with miR-21 mimic into 293T-HEK cells, the luciferase activity was attenuated by 43 ± 13% compared to cells cotransfected with miR-67 mimic (n=4; P<0.02; Fig. 3C).”

  • The paper relies on this without support.

    Antisense inhibition reduces endogenous miR-21 levels in cultured neurons.

    “attenuation of endogenous miR-21 by antisense inhibition exacerbated cell death after OGD.”

  • The paper relies on this without support.

    Transfection with miR-21 mimic increases functional miR-21 levels in cultured neurons.

    “overexpression of miR-21 in cultured cortical neurons substantially suppressed oxygen and glucose deprivation (OGD)-induced apoptotic cell death”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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.

  • Live/dead assay is described as both significant and insignificant

    Major

    The results report a significantly higher proportion of dead cells with miR-21 inhibition and give P<0.05 for the live/dead assay, but later describe the live/dead data as statistically insignificant.

  • Cited siRNA study targets Fas, not Faslg

    Minor

    The discussion says Hamar et al. targeted Faslg, whereas the paper's own reference title says the siRNA targeted Fas. The text identifies Fas as the receptor for FASLG, so these are different targets.

2 of 2

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Related

Authors
Buller, B., Liu, X., Wang, X., Zhang, R. L., Zhang, L., Hozeska‐Solgot, A., Chopp, M., & Zhang, Z. G.
Affiliations
  • Henry Ford Hospital (US)
  • Oakland University (US)
ORCID
Venue
The FEBS Journal
Publisher
Wiley
Published
2010-09-14
Volume
277
Issue
20
Pages
4299-4307
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
DOI
10.1111/j.1742-4658.2010.07818.x
PMC
PMC2957309
OpenAlex
W1557444671
Semantic Scholar
dc4b4e4f4771a194e0af3821f06772f48410e241
Cited by
242
References
36
Citations by year
2026: 7 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 22 · 2020: 20 · 2019: 20 · 2018: 17 · 2017: 24 · 2016: 21 · 2015: 16 · 2014: 17 · 2013: 24 · 2012: 11
FWCI
4.06
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • FEBS Journal (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • American Heart Association
  • National Heart, Lung, and Blood Institute (R01 HL064766, R01HL64766)
  • National Institute of Neurological Disorders and Stroke (P01NS42345, R01 NS062832, P01 NS042345)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
miR-21, stroke, cerebral ischemia, neuronal apoptosis, neuroprotection, Fas ligand, oxygen-glucose deprivation, 3' UTR targeting, antisense inhibition
MeSH terms
Animals, Gene Expression Regulation, Ischemia, Neurons, Cell Death, Rats, Wistar, Protective Agents, Stroke, MicroRNAs, Rats, Fas Ligand Protein

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