MicroRNA-31-5p attenuates doxorubicin-induced cardiotoxicity via quaking and circular RNA Pan3

Journal of Molecular and Cellular Cardiology
Xiaoyu JiJianxun Wang

Abstract

Doxorubicin (DOX) is a broad-spectrum anticancer drug with considerable cardiotoxicity. DOX can induce myocardial apoptosis by modulating multiple signalling pathways. A better understanding of the underlying mechanism of DOX's cardiotoxicity will improve its clinical application and help avoid heart failure in patients. Models of DOX cardiotoxicity in cultured cardiomyocytes and mice were used. Cell death was determined by TUNEL and caspase 3/7 activity assay. Quaking (QKI) expression was detected by immunoblotting; microRNA-31-5p and circular RNA (circRNA) levels were determined by qRT-PCR. Luciferase reporter assays were performed to validate the miR-31-5p target. We found that DOX treatment upregulated miR-31-5p expression both in cultured cardiomyocytes and in mouse heart tissue. Silencing of miR-31-5p significantly alleviated the myocardial apoptosis induced by DOX treatment both in vivo and in vitro. Further analysis indicated QKI as a direct target of miR-31-5p, which has been reported to influence circRNA expression in a series of cell types. We found that circPan3 was specifically downregulated in cardiomyocytes upon DOX treatment. We further confirmed that the downregulation of circPan3 was due to the silencing of QK...Continue Reading

Citations

May 21, 2020·Cells·Ying Wang, Bin Liu
Jan 24, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Qiwei YangBurton B Yang
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Wan-Li JiangSong-Ping Xie
May 1, 2021·Frontiers in Cardiovascular Medicine·Ling TangWuqiang Zhu
Oct 17, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jason R Brown, Arul M Chinnaiyan
Jul 6, 2021·Frontiers in Cell and Developmental Biology·Xinyun ChenWeinian Shou
Jul 13, 2021·Frontiers in Cardiovascular Medicine·Tiqun YangZhan-Peng Huang

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