# The Role of miRNAs in Chemotherapy-Induced Cardiotoxicity

## TL;DR

This paper reviews how microRNAs (miRNAs) are involved in chemotherapy-induced heart damage and could help detect and treat it early.

## Contribution

The paper systematically summarizes miRNAs associated with chemotherapy-related cardiac dysfunction and their potential as biomarkers and therapeutic targets.

## Key findings

- Several miRNAs, including miR-1, miR-29, and miR-30, are linked to apoptosis and oxidative stress in chemotherapy-induced cardiotoxicity.
- miRNAs like let-7, miR-34a, and miR-499 are associated with fibrosis and extracellular matrix remodeling in cardiac dysfunction.
- miR-130a is highlighted as a potential therapeutic agent for chemotherapy-related cardiac dysfunction.

## Abstract

Cardiotoxicity is one of the most important adverse events of chemotherapy regimens, especially of anthracyclines. Different mechanisms are associated with chemotherapy-related cardiac dysfunction (CTRCD): oxidative stress, mitochondrial dysfunction, inhibition of topoisomerase 2 beta, abnormal iron metabolism, apoptosis, and fibrosis. Even after years of investigation, the early detection and prevention of cardiac impairment after chemotherapy through biomarkers remains an unmet need. The differential expression of microRNAs (miRs) in plasma at different timepoints (baseline, stable intervals during and at the end of chemotherapy) has been associated with CTRCD. Namely, some miRs, such as let-7, miR-29 and miR-30 family, miR-1 clusters, miR-34a, miR-126, miR-130a, miR-140, miR-320a, and miR-499, could play prognostic and/or diagnostic roles in CTRCD. Key miRs involved in apoptosis and oxidative stress include miR-1, miR-21, miR-30 and miR-130a, while let-7 family, miR-34a, miR-29b and miR-499 are associated with fibrosis and extracellular matrix remodeling. Additionally, mitochondrial function is regulated by miR-30, miR-130a and miR-499. Expanding its role, miR-130a could act as a therapeutic agent of CTRCD through its inhibition. This narrative review focuses on the current understanding of miRs’ involvement in CTRCD pathophysiology, summarizes the evidence linking miRs with cardiotoxicity risk, and explores the potential of miRs as biomarkers and therapeutic targets to improve early detection, risk stratification, and management of CTRCD.