hsa_circ_0005232在放疗损伤心肌细胞中的作用机制研究

Radiotherapy is one of the most commonly used methods for treating malignant tumors. When radiotherapy is performed on a malignant tumor of the chest or abdomen, the heart in the mediastinum is also irradiated, causing heart damage, it's called radiation-induced heart disease (RIHD). For most cancer patients who received radiotherapy, the treatment and recovery have been seriously affected because of radiation-induced cardiovascular disease. Meanwhile, the molecular mechanism and regulation of RIHD is not clear, so there is still no effective method for the treatment of RIHD. circRNA closely associated with cardiomyocytes radiation damage repair. In our previous study, we found that the expression of hsa_circ_0005232 is higher in cardiomyocytes, and significantly increased when cardiomyocytes under stress treatment. This research attempts to use hsa_circ_0005232 as entry point, to study the molecular mechanisms and the regulatory role of circRNA in cardiomyocytes after radiation injury, at a cellular level and in animals. The completion of this subject will provide new theoretical basis for understanding and reducing the radiation damage.

放射治疗是当今治疗恶性肿瘤最常用的方法之一。在对胸腹部等恶性肿瘤进行放射治疗时，位于纵膈的心脏由于受到照射而引起心脏损伤，统称为放射性心脏病。放射治疗引发的心血管疾病，已经严重影响了肿瘤病人的治疗和康复。同时，由于放射性心脏病发生和调控的分子机制尚不明确，所以目前尚无有效的治疗放射性心脏病的方法。circRNA与心肌细胞放射损伤修复的关系密切。我们前期研究发现，hsa_circ_0005232在心肌细胞中高表达，并且在心肌细胞受到胁迫处理时显著上调。本研究拟以hsa_circ_0005232为研究切入点，在细胞和动物水平深入研究circRNA在放射损伤心肌细胞中的分子机制和调控作用。本课题的完成将为放射后心肌细胞损伤修复分子机制的研究提供新的思路，为提高放疗效果和放疗后恢复提供重要的理论依据。

放射治疗是当今治疗恶性肿瘤最常用的方法之一。在对胸腹部等恶性肿瘤进行放射治疗时，位于纵膈的心脏由于受到照射而引起心脏损伤，统称为放射性心脏病。放射治疗引发的心血管疾病，已经严重影响了肿瘤病人的治疗和康复。放射性心脏病发生和调控的分子机制尚不明确，目前尚无有效的治疗放射性心脏病的方法。本研究发现，hsa_circ_0005232在心肌细胞中高表达，并且在心肌细胞受到胁迫处理时显著下调。在对线虫模型进行放疗损伤研究中发现高剂量放疗射线可诱导线虫GCY,LSM,GST,PLC-3,AGE-1LIN-45,CBP-1等家族的异常表达；对小鼠进行放疗损伤研究发现，hsa_circ_0005232在放射治疗损伤模型中异常低表达，可能通过抑制FUS/PDI进入线粒体从而介导细胞自噬和细胞放疗损伤。该研究可为心脏放疗损伤的临床保护和应用提供重要理论依据。