Abstract |
Circular RNAs ( circRNAs) are essential regulators associated with many cardiac conditions, including myocardial infarction (MI). This study aimed to explore circRNA expression during MI development in an animal model and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Microarray and real-time quantitative PCR showed that the circRNA PVT1 (circPVT1) was expressed at high levels in MI tissues and H/R-triggered cardiomyocytes. Loss-of-function assays were utilized for examining the influence of circPVT1 on cardiac function and cardiomyocyte properties. Cardiac function was measured by echocardiography at 7 d after MI. Reduced circPVT1 expression significantly decreased MI-triggered myocardial infarct size by 60% and prevented MI-triggered reductions in fractional shortening (%FS) and ejection fraction (EF%). Results of LDH, CCK-8, EdU staining, colony formation assays, and flow cytometry showed that circPVT1 silencing restored cell viability and proliferation while decreased apoptosis. Mechanistic experiments indicated that microRNAs (miR)-125b and miR-200a associated with circPVT1. We demonstrated that circPVT1 functioned as a competitive endogenous RNA ( ceRNA) to sponge both miR-125b and miR-200a. Gain-of-function assays showed that miR-125b and miR-200a upregulation partially eliminated the effects of circPVT1 on cardiomyocyte properties. In addition, we found that the previously reported p53/ TRAF6, SIRT7, Keap1/Nrf2, and PDCD4 pathways were regulated by the circPVT1/miR-125b/miR-200a axis. In conclusion, our study suggests that circPVT1 protects the myocardium from MI and H/R injury by preventing miR-125b- and miR-200a-mediated apoptotic signaling.
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Authors | Cheng Luo, Guo-Xing Ling, Bin-Feng Lei, Xu Feng, Xiao-Yong Xie, Chen Fang, Yu-Gui Li, Xiong-Wei Cai, Bao-Shi Zheng |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 159
Pg. 80-90
(10 2021)
ISSN: 1095-8584 [Electronic] England |
PMID | 34097926
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 Elsevier Ltd. All rights reserved. |
Chemical References |
- MicroRNAs
- Mirn125 microRNA, mouse
- Mirn200 microRNA, mouse
- PVT1 long-non-coding RNA, mouse
- RNA, Circular
- RNA, Long Noncoding
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Topics |
- Animals
- Apoptosis
(genetics)
- Cell Proliferation
(genetics)
- Cell Survival
(genetics)
- Male
- Mice
- Mice, Inbred BALB C
- MicroRNAs
(genetics)
- Myocardium
(metabolism)
- Myocytes, Cardiac
(metabolism)
- RNA Interference
(physiology)
- RNA, Circular
(genetics)
- RNA, Long Noncoding
(genetics)
- Rats
- Reperfusion Injury
(genetics)
- Signal Transduction
(genetics)
- Up-Regulation
(genetics)
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