Department of Cardiology, Fujian Longyan People's Hospital, Longyan, Fujian 364000, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2020.11816. Epub 2021 Jan 5.
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.
放射治疗是癌症的主要治疗方法之一,可导致心脏损伤延迟。环状 RNA(circRNA)circFOXO3(hsa_circ_0006404)与癌症进展有关。然而,circFOXO3 在放射性心脏毒性中的作用尚不清楚。本研究旨在确定 circFOXO3 在放射性心脏毒性中的作用。本研究建立了 circFOXO3 敲低(KD)或过表达(OE)的心肌细胞。功能测定结果表明,心肌细胞中 circFOXO3 的 KD 可显著增加放射后的 DNA 损伤和细胞凋亡。相比之下,circFOXO3 的 OE 降低了对辐射的 DNA 损伤和细胞凋亡率。机制上,circFOXO3 的 KD 可上调 Bax、caspase-3 和 caspase-7 的水平,并降低 Bcl-2 的表达,而 circFOXO3 的 OE 则降低了 Bax、caspase-3 和 caspase-7 的表达,并增加了 Bcl-2 的表达。因此,本研究表明,circFOXO3 通过减少 DNA 损伤和细胞凋亡来保护心肌细胞免受放射引起的心脏毒性。circFOXO3 可能是一种针对放射性心脏毒性的潜在治疗靶点。