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

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.

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Fig. 1: NcRNAs involved in different mechanisms of DOX-induced cardiac cell apoptosis.

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Acknowledgements

This work was supported by the Natural Science Foundation of Shandong Province (Grant no. JQ201815), National Natural Science Foundation of China (Grant no. 81770232), and a grant from Fu Wai Hospital (No. 2019kf-03).

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Correspondence to Jian-xun Wang.

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Fa, Hg., Chang, Wg., Zhang, Xj. et al. Noncoding RNAs in doxorubicin-induced cardiotoxicity and their potential as biomarkers and therapeutic targets. Acta Pharmacol Sin 42, 499–507 (2021). https://doi.org/10.1038/s41401-020-0471-x

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Keywords

  • noncoding RNAs
  • doxorubicin
  • cardiotoxicity
  • biomarkers

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