Review Article

Noncoding RNAs in doxorubicin-induced cardiotoxicity and their potential as biomarkers and therapeutic targets

Authors: Hong-ge Fa1,2, Wen-guang Chang2, Xue-juan Zhang3, Dan-dan Xiao1,2, Jian-xun Wang1
1 School of Basic Medical Sciences, Qingdao University, Qingdao 266021, China
2 Institute for Translational Medicine, Qingdao University, Qingdao 266021, China
3 Department of General Practice, Affiliated Hospital, Qingdao University, Qingdao 266021, China
Correspondence to: Jian-xun Wang: wangjx@qdu.edu.cn,
DOI: 10.1038/s41401-020-0471-x
Received: 9 March 2020
Accepted: 3 July 2020
Advance online: 21 July 2020

Abstract

Anthracyclines, such as doxorubicin (DOX), are well known for their high efficacy in treating multiple cancers, but their clinical usage is limited due to their potential to induce fatal cardiotoxicity. Such detrimental effects significantly impact the overall physical condition or even induce the morbidity and mortality of cancer survivors. Therefore, it is extremely important to understand the mechanisms of DOX-induced cardiotoxicity to develop methods for the early detection of cytotoxicity and therapeutic applications. Studies have shown that many molecular events are involved in DOX-induced cardiotoxicity. However, the precise mechanisms are still not completely understood. Recently, noncoding RNAs (ncRNAs) have been extensively studied in a diverse range of regulatory roles in cellular physiological and pathological processes. With respect to their roles in DOX-induced cardiotoxicity, microRNAs (miRNAs) are the most widely studied, and studies have focused on the regulatory roles of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), which have been shown to have significant functions in the cardiovascular system. Recent discoveries on the roles of ncRNAs in DOX-induced cardiotoxicity have prompted extensive interest in exploring candidate ncRNAs for utilization as potential therapeutic targets and/or diagnostic biomarkers. This review presents the frontier studies on the roles of ncRNAs in DOX-induced cardiotoxicity, addresses the possibility and prospects of using ncRNAs as diagnostic biomarkers or therapeutic targets, and discusses the possible reasons for related discrepancies and limitations of their use.
Keywords: noncoding RNAs; doxorubicin; cardiotoxicity; biomarkers

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