miR-181c-5p Exacerbates HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4
Joint Authors
Cai, Yin
Ma, Haichun
Yan, Dan
Xu, Aimin
Zhang, Dengwen
Ge, Liang
Ying, Fan
Liu, Hao
He, Yanjing
Pang, Lei
Xia, Zhengyuan
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-17
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Background.
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.
American Psychological Association (APA)
Ge, Liang& Cai, Yin& Ying, Fan& Liu, Hao& Zhang, Dengwen& He, Yanjing…[et al.]. 2019. miR-181c-5p Exacerbates HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1202426
Modern Language Association (MLA)
Ge, Liang…[et al.]. miR-181c-5p Exacerbates HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1202426
American Medical Association (AMA)
Ge, Liang& Cai, Yin& Ying, Fan& Liu, Hao& Zhang, Dengwen& He, Yanjing…[et al.]. miR-181c-5p Exacerbates HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1202426
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202426