# Cardiomyocyte overexpression of microRNA-210 mitigates apoptotic cell death induced by doxorubicin

## TL;DR

This study shows that increasing miR-210 in heart cells reduces cell death caused by doxorubicin, a chemotherapy drug known to damage the heart.

## Contribution

The study demonstrates a novel cardioprotective role of miR-210 against doxorubicin-induced apoptosis in cardiomyocytes.

## Key findings

- Overexpression of miR-210 significantly reduces doxorubicin-induced cell death in AC-16 cardiomyocytes.
- miR-210 modulates the Akt-GSK-3β signaling pathway to inhibit apoptosis in doxorubicin-treated cells.
- Downregulation of miR-210 increases apoptotic cell death in cardiomyocytes exposed to doxorubicin.

## Abstract

Advancements in cancer diagnostics and treatments have significantly increased patient survival rates. However, these advancements are often accompanied by treatment-induced health issues. Among these, chemotherapy-induced cardiac damage is particularly concerning, with doxorubicin being notably cardiotoxic. Despite extensive research, effective strategies to protect the heart from doxorubicin-induced cardiotoxicity remain elusive. This study aims to investigate whether miR-210, which has previously shown cardioprotective properties against ischemic heart disease, can offer protection against doxorubicin-induced cardiotoxicity.

miR-210 was upregulated or downregulated in AC-16 cardiomyocytes using transient expression or decoy/inhibitory transfection vectors before being subjected to 5 µM doxorubicin treatment for 24 h. Cell death was determined using a lactate dehydrogenase release assay. Apoptotic cell death was determined by a caspase-3 activity assay, and the Akt-GSK-3β signaling pathway was explored using a sandwich enzyme-linked immunosorbent assay (ELISA) approach.

Overexpression of miR-210 in AC-16 cardiomyocytes exposed to 24 h of doxorubicin treatment caused a significant reduction in cell death and a significant reduction in apoptotic cell death, measured by caspase-3 activity. Downregulation of miR-210 in AC-16 cardiomyocytes exposed to the same conditions resulted in a significant increase in apoptotic cell death. An increase in phosphorylation of GSK-3β at the inhibitory p-Ser9 site and the Akt activating site p-Ser473 was observed in the miR-210 overexpression group, while a decrease in p-Ser473 Akt but no difference in p-Ser9 GSK-3β was observed in the miR-210-downregulated group.

miR-210 exerts cardioprotective effects in AC-16 cardiomyocytes exposed to 24 h of doxorubicin treatment by reducing cell death and inhibiting caspase-3 dependent apoptosis through modulation of the Akt-GSK-3β signaling pathway. This study suggests a novel role for miR-210 in mitigating DOX-induced cardiomyocyte death, potentially laying the foundation for new treatment strategies.