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Conference Paper: MicroRNA-17-3p inhibits excessive post-hypoxic autophagy and attenuates H9C2 cardiomyocytes reoxygenation injury via PTEN-Akt-mTOR signaling

TitleMicroRNA-17-3p inhibits excessive post-hypoxic autophagy and attenuates H9C2 cardiomyocytes reoxygenation injury via PTEN-Akt-mTOR signaling
Authors
Issue Date2018
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
Experimental Biology 2018 Meeting, San Diego, CA, 21-25 April 2018 in The FASEB Journal, 2018, v. 32 n. 1, suppl., p. abstract no. lb595 How to Cite?
AbstractBackgroundThe microRNA (miR)-17~92 is one of the best-characterized polycistronic miRNA clusters, which encodes six individual miRNAs and contributes to various cellular and biological processes. In particular, miR-17-3p (a passenger miRNA of miR-17) has been shown to indirectly inhibit Phosphatase and tensin homolog (PTEN) and attenuate myocardial ischemia/reperfusion (I/R) injury, but the underneath mechanism is unclear. Inhibition of PTEN can upregulate Akt/mTOR signaling and therefore suppresses the excessive autophagy, which may be a mechanism that underlies myocardial I/R injury. We, thus, hypothesized that miR-17-3p may protect against hypoxia/reoxygenation (H/R) induced cell injury by inhibiting post-hypoxic excessive autophagy in H9C2 cardiomyocytes via PTEN-Akt-mTOR signaling pathway.Methods and resultsIn rat H9C2 cardiomyocytes, H/R (6 hours hypoxia followed by 6 hours reoxygenation) significantly enhanced the expression of miR-17-3p (P <0.05 vs. Control), which was concomitant by increased lactic acid dehydrogenase (LDH) leakage (cell injury marker, P<0.05 vs. Control) and the levels of p62 and the ratio of LC3II/I (autophagy markers, P<0.05 vs. Control), suggesting that miR-17-3p may be involved in the pathogenesis of H/R induced autophagic cell death. To explore the potential role of miR-17-3p in H/R-induced cell injury, H9C2 cells were transfected with the miR-17-3p agomir or its negative control. The overexpression of miR-17-3p can significantly attenuate H/R-induced cell injury (reduced LDH level, P <0.05 vs. H/R) and inhibit H/R-induced excessive autophagy (decreased levels of p62 and LC3II/I, P <0.05 vs. H/R). Given the important role of PTEN-Akt-mTOR signaling in autophagy, the effects of miR-17-3p on the key events in the PTEN-Akt-mTOR signaling cascade during H/R were examined. As anticipated, miR-17-3p overexpression significantly down-regulated PTEN expression and up-regulated the levels of phosphorylated Akt1 (Thr308) and mTOR (P<0.05 vs. H/R), indicating that the miR-17-3p may protect against excessive post-hypoxic autophagic cell death in H9C2 cardiomyocytes via PTEN-Akt-mTOR signaling pathway.ConclusionUpregulating PTEN-Akt-mTOR axis and the subsequent inhibition of excessive autophagy may represent the major mechanism whereby miR-17-3p attenuates H/R injury in H9C2 cardiomyocytes.
DescriptionAbstract
Persistent Identifierhttp://hdl.handle.net/10722/263979
ISSN
2017 Impact Factor: 5.595
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorHe, Y-
dc.contributor.authorCai, Y-
dc.contributor.authorYAN, D-
dc.contributor.authorZhang, D-
dc.contributor.authorChen, C-
dc.contributor.authorIrwin, MG-
dc.contributor.authorWang, S-
dc.contributor.authorXia, Z-
dc.date.accessioned2018-10-22T07:47:34Z-
dc.date.available2018-10-22T07:47:34Z-
dc.date.issued2018-
dc.identifier.citationExperimental Biology 2018 Meeting, San Diego, CA, 21-25 April 2018 in The FASEB Journal, 2018, v. 32 n. 1, suppl., p. abstract no. lb595-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/263979-
dc.descriptionAbstract-
dc.description.abstractBackgroundThe microRNA (miR)-17~92 is one of the best-characterized polycistronic miRNA clusters, which encodes six individual miRNAs and contributes to various cellular and biological processes. In particular, miR-17-3p (a passenger miRNA of miR-17) has been shown to indirectly inhibit Phosphatase and tensin homolog (PTEN) and attenuate myocardial ischemia/reperfusion (I/R) injury, but the underneath mechanism is unclear. Inhibition of PTEN can upregulate Akt/mTOR signaling and therefore suppresses the excessive autophagy, which may be a mechanism that underlies myocardial I/R injury. We, thus, hypothesized that miR-17-3p may protect against hypoxia/reoxygenation (H/R) induced cell injury by inhibiting post-hypoxic excessive autophagy in H9C2 cardiomyocytes via PTEN-Akt-mTOR signaling pathway.Methods and resultsIn rat H9C2 cardiomyocytes, H/R (6 hours hypoxia followed by 6 hours reoxygenation) significantly enhanced the expression of miR-17-3p (P <0.05 vs. Control), which was concomitant by increased lactic acid dehydrogenase (LDH) leakage (cell injury marker, P<0.05 vs. Control) and the levels of p62 and the ratio of LC3II/I (autophagy markers, P<0.05 vs. Control), suggesting that miR-17-3p may be involved in the pathogenesis of H/R induced autophagic cell death. To explore the potential role of miR-17-3p in H/R-induced cell injury, H9C2 cells were transfected with the miR-17-3p agomir or its negative control. The overexpression of miR-17-3p can significantly attenuate H/R-induced cell injury (reduced LDH level, P <0.05 vs. H/R) and inhibit H/R-induced excessive autophagy (decreased levels of p62 and LC3II/I, P <0.05 vs. H/R). Given the important role of PTEN-Akt-mTOR signaling in autophagy, the effects of miR-17-3p on the key events in the PTEN-Akt-mTOR signaling cascade during H/R were examined. As anticipated, miR-17-3p overexpression significantly down-regulated PTEN expression and up-regulated the levels of phosphorylated Akt1 (Thr308) and mTOR (P<0.05 vs. H/R), indicating that the miR-17-3p may protect against excessive post-hypoxic autophagic cell death in H9C2 cardiomyocytes via PTEN-Akt-mTOR signaling pathway.ConclusionUpregulating PTEN-Akt-mTOR axis and the subsequent inhibition of excessive autophagy may represent the major mechanism whereby miR-17-3p attenuates H/R injury in H9C2 cardiomyocytes.-
dc.languageeng-
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/-
dc.relation.ispartofThe FASEB Journal-
dc.titleMicroRNA-17-3p inhibits excessive post-hypoxic autophagy and attenuates H9C2 cardiomyocytes reoxygenation injury via PTEN-Akt-mTOR signaling-
dc.typeConference_Paper-
dc.identifier.emailCai, Y: caidavid@hku.hk-
dc.identifier.emailZhang, D: gzdw@hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityIrwin, MG=rp00390-
dc.identifier.authorityXia, Z=rp00532-
dc.identifier.hkuros295400-
dc.identifier.volume32-
dc.identifier.issue1, suppl.-
dc.identifier.spageabstract no. lb595-
dc.identifier.epageabstract no. lb595-
dc.publisher.placeUnited States-

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