circFOXO3 protects cardiomyocytes against radiation-induced cardiotoxicity

Abstract

Radiation therapy, one of the major treatment options for cancer, can cause delayed heart damage. The circular RNA (circRNA) circFOXO3 (hsa_circ_0006404) is associated with cancer progression. However, the functions of circFOXO3 in radiation-induced cardiotoxicity remains unknown. The present study aimed to identify the functions of cirFOXO3 in radiation-induced cardiotoxicity. The present study established circFOXO3-knockdown (KD) or -overexpressing (OE) cardiomyocytes. Functional assay results showed that KD of circFOXO3 in cardiomyocytes significantly increased DNA damage and apoptosis after radiation. By contrast, OE of circFOXO3 reduced DNA damage and apoptosis rates in response to radiation. Mechanistically, KD of circFOXO3 elevated the levels of Bax, caspase 3 and caspase 7, and decreased Bcl-2 expression, whereas OE of circFOXO3 decreased Bax, caspase 3 and caspase 7 expression, and increased Bcl-2 expression. Thus, the present study indicated that circFOXO3 protected cardiomyocytes from radiation-induced cardiotoxicity by reducing DNA damage and apoptosis. circFOXO3 may be a potential therapeutic target against radiation-induced cardiotoxicity.