RING Finger Protein 10 Regulates AP-1/Meox2 to Mediate Pirarubicin-Induced Cardiomyocyte Apoptosis

Abstract

Pirarubicin (THP) is one of the classic chemotherapy drugs for cancer treatment. It is often clinically limited because of its cardiotoxicity. The occurrence and development of THP-mediated chemotherapy-related cardiotoxicity (CRC) may be reversed by RING finger protein 10 (RNF10). This study was performed with the aim of evaluating the inhibitory effect of RNF10 on THP-mediated CRC and its molecular mechanism. In vivo, we found that the expression of RNF10 decreased in THP-induced CRC rats, accompanied by Meox2 inhibition and AP-1 activation, resulting in increased cardiomyocyte apoptosis. After small interfering RNA (siRNA) and lentivirus transfection (Lv) of RNF10 in vitro, the expression of RNF10, Meox2, and AP-1 proteins and the degree of cardiomyocyte apoptosis were detected. We found that overexpression of RNF10 in H9C2 cardiomyocytes significantly promoted Meox2 and inhibited AP-1, alleviated apoptosis, and showed further inhibitory activity on THP-induced cardiomyocyte toxicity. Silencing RNF10 showed the opposite result. Our study showed that RNF10 inhibited THP-induced CRC through the activity of Meox2 and AP-1 proteins. RNF10 may be the next drug target for the treatment of CRC and other related cardiovascular diseases.