摘要
目的:探讨蒽环类药物诱导心肌毒性的机制和新的治疗靶点。方法:106例乳腺癌患者根据超声心动图检查鉴别出肿瘤治疗相关心功能障碍,分为心功能障碍组及对照组。通过微阵列技术高通量筛选两组患者差异表达miRNA。体外构建蒽环类药物诱导H9C2心肌细胞损伤模型,通过调控miR-25a-5p的表达,观察miR-25a-5p在蒽环类药物诱导H9C2心肌细胞损伤中的作用。结果:乳腺癌患者中9例发生肿瘤治疗相关心功能障碍,并从两组患者中鉴定出9个差异表达的miRNA。其中8个miRNA在体外模型中进一步得到验证,尤其是miR-25a-5p。通过上调miR-25a-5p,可进一步加重蒽环类药物诱导心肌细胞氧化损伤。结论:miR-25a-5p促进蒽环类药物诱导的心肌损伤,可能是新的生物标志物及治疗靶点。
Objective:To explore the mechanism and new therapeutic targets of anthracycline-induced cardiotoxicity.Methods:A total of 106 cases of breast cancer patients were divided into cardiac dysfunction group and control group based on echocardiography to identify cancer therapeutics-related cardiac functional impairment.Differentially expressed miRNAs between the two groups were screened out by high-throughput microarray technology.The model of H9C2 myocardial cell damage induced by anthracyclines was constructed in vitro,and the role of miR-25a-5p in the H9C2 myocardial cell damage induced by anthracyclines was observed by regulating the expression of miR-25a-5p.Results:Cancer therapeutics-related cardiac dysfunction occurred in 9 breast cancer patients,and a total of 9 differentially expressed miRNAs were identified between the two groups.Eight of these miRNAs were further validated in vitro model,especially miR-25a-5p.Up-regulation of miR-25a-5p could further aggravate the anthracycline-induced oxidative damage in myocardial cells.Conclusion:The miR-25a-5p aggravates anthracycline-induced myocardial damage and may be a new biomarker and therapeutic target.
作者
刘睿
吕雨桐
姜翠红
王高兴
赵志正
LIU Rui;LYU Yutong;JIANG Cuihong;WANG Gaoxing;ZHAO Zhizheng(Department of Oncology,South District of Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 102618,China;Department of Oncology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)
出处
《广西医科大学学报》
CAS
2024年第1期26-31,共6页
Journal of Guangxi Medical University
基金
国家自然科学基金资助项目(No.81703918)
中国中医科学院广安门医院南区院级科研基金项目(No.Y2020-03)。
