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Article: miR-181c-5p Exacerbates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4

TitlemiR-181c-5p Exacerbates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4
Authors
Issue Date2019
PublisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/
Citation
Oxidative Medicine and Cellular Longevity, 2019, v. 2019, p. article no. 1957920 How to Cite?
AbstractBackground. Activation of cell apoptosis is a major form of cell death during myocardial ischemia/reperfusion injury (I/RI). Therefore, examining ways to control cell apoptosis has important clinical significance for improving postischemic recovery. Clinical evidence demonstrated that miR-181c-5p was significantly upregulated in the early phase of myocardial infarction. However, whether or not miR-181c-5p mediates cardiac I/RI through cell apoptosis pathway is unknown. Thus, the present study is aimed at investigating the role and the possible mechanism of miR-181c-5p in apoptosis during I/R injury by using H9C2 cardiomyocytes. Methods and Results. The rat origin H9C2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R, 6 hours hypoxia followed by 6 hours reoxygenation) to induce cell injury. The results showed that H/R significantly increased the expression of miR-181c-5p but not miR-181c-3p in H9C2 cells. In line with this, in an in vivo rat cardiac I/RI model, miR-181c-5p expression was also significantly increased. The overexpression of miR-181c-5p by its agomir transfection significantly aggravated H/R-induced cell injury (increased lactate dehydrogenase level and reduced cell viability) and exacerbated H/R-induced cell apoptosis (greater cleaved caspases 3 expression, Bax/Bcl-2 and more TUNEL-positive cells). In contrast, inhibition of miR-181c-5p in vitro had the opposite effect. By using computational prediction algorithms, protein tyrosine phosphatase nonreceptor type 4 (PTPN4) was predicted as a potential target gene of miR-181c-5p and was verified by the luciferase reporter assay. The overexpression of miR-181c-5p significantly attenuated the mRNA and protein expression of PTPN4 in H9C2 cardiomyocytes. Moreover, knockdown of PTPN4 significantly aggravated H/R-induced enhancement of LDH level, cleaved caspase 3 expression, and apoptotic cell death, which mimicked the proapoptotic effects of miR-181c-5p in H9C2 cardiomyocytes. Conclusions. These findings suggested that miR-181c-5p exacerbates H/R-induced cardiomyocyte injury and apoptosis via targeting PTPN4 and that miR-181c-5p/PTPN4 signaling may yield novel strategies to combat myocardial I/R injury.
Persistent Identifierhttp://hdl.handle.net/10722/293530
ISSN
2019 Impact Factor: 5.076
2015 SCImago Journal Rankings: 1.503
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGe, L-
dc.contributor.authorCai, Y-
dc.contributor.authorYing, F-
dc.contributor.authorLiu, H-
dc.contributor.authorZhang, D-
dc.contributor.authorHE, Y-
dc.contributor.authorPang, L-
dc.contributor.authorYAN, D-
dc.contributor.authorXu, A-
dc.contributor.authorMa, H-
dc.contributor.authorXia, Z-
dc.date.accessioned2020-11-23T08:18:05Z-
dc.date.available2020-11-23T08:18:05Z-
dc.date.issued2019-
dc.identifier.citationOxidative Medicine and Cellular Longevity, 2019, v. 2019, p. article no. 1957920-
dc.identifier.issn1942-0900-
dc.identifier.urihttp://hdl.handle.net/10722/293530-
dc.description.abstractBackground. Activation of cell apoptosis is a major form of cell death during myocardial ischemia/reperfusion injury (I/RI). Therefore, examining ways to control cell apoptosis has important clinical significance for improving postischemic recovery. Clinical evidence demonstrated that miR-181c-5p was significantly upregulated in the early phase of myocardial infarction. However, whether or not miR-181c-5p mediates cardiac I/RI through cell apoptosis pathway is unknown. Thus, the present study is aimed at investigating the role and the possible mechanism of miR-181c-5p in apoptosis during I/R injury by using H9C2 cardiomyocytes. Methods and Results. The rat origin H9C2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R, 6 hours hypoxia followed by 6 hours reoxygenation) to induce cell injury. The results showed that H/R significantly increased the expression of miR-181c-5p but not miR-181c-3p in H9C2 cells. In line with this, in an in vivo rat cardiac I/RI model, miR-181c-5p expression was also significantly increased. The overexpression of miR-181c-5p by its agomir transfection significantly aggravated H/R-induced cell injury (increased lactate dehydrogenase level and reduced cell viability) and exacerbated H/R-induced cell apoptosis (greater cleaved caspases 3 expression, Bax/Bcl-2 and more TUNEL-positive cells). In contrast, inhibition of miR-181c-5p in vitro had the opposite effect. By using computational prediction algorithms, protein tyrosine phosphatase nonreceptor type 4 (PTPN4) was predicted as a potential target gene of miR-181c-5p and was verified by the luciferase reporter assay. The overexpression of miR-181c-5p significantly attenuated the mRNA and protein expression of PTPN4 in H9C2 cardiomyocytes. Moreover, knockdown of PTPN4 significantly aggravated H/R-induced enhancement of LDH level, cleaved caspase 3 expression, and apoptotic cell death, which mimicked the proapoptotic effects of miR-181c-5p in H9C2 cardiomyocytes. Conclusions. These findings suggested that miR-181c-5p exacerbates H/R-induced cardiomyocyte injury and apoptosis via targeting PTPN4 and that miR-181c-5p/PTPN4 signaling may yield novel strategies to combat myocardial I/R injury.-
dc.languageeng-
dc.publisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/-
dc.relation.ispartofOxidative Medicine and Cellular Longevity-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titlemiR-181c-5p Exacerbates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4-
dc.typeArticle-
dc.identifier.emailCai, Y: caidavid@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1155/2019/1957920-
dc.identifier.pmid31178952-
dc.identifier.pmcidPMC6501226-
dc.identifier.hkuros319855-
dc.identifier.volume2019-
dc.identifier.spagearticle no. 1957920-
dc.identifier.epagearticle no. 1957920-
dc.identifier.isiWOS:000466482500001-
dc.publisher.placeUnited States-

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