Mitigation of Doxorubicin-Induced Cardiotoxicity in Lymphoma Patients Using Synergistic miRNA Combinations Identified Through Combinatorial Genetics en masse (CombiGEM)

Abstract Doxorubicin, a cornerstone in lymphoma treatment, is associated with significant cardiotoxicity, limiting its therapeutic potential. This study explores the use of Combinatorial Genetics en masse (CombiGEM) to identify synergistic microRNA (miRNA) combinations, specifically miR-222 and miR-455, for mitigating doxorubicin-induced cardiotoxicity in lymphoma patients. Using in vitro cardiomyocyte models and in vivo lymphoma mouse models, we demonstrate that this miRNA combination reduces oxidative stress, preserves mitochondrial function, and attenuates cardiac dysfunction. These findings suggest a novel cardioprotective strategy, warranting further clinical validation in lymphoma cohorts. Keywords: Doxorubicin, cardiotoxicity, lymphoma, microRNA, CombiGEM, cardioprotection摘要 阿霉素（Doxorubicin）是淋巴瘤治疗的核心基石药物，但其伴随的严重心脏毒性极大限制了其治疗潜力。本研究采用群体组合遗传学（Combinatorial Genetics en masse，CombiGEM）技术筛选协同性微小RNA（miRNA）组合，最终确定miR-222与miR-455的联合方案，用于缓解淋巴瘤患者体内阿霉素诱导的心脏毒性。本研究通过体外心肌细胞模型与体内淋巴瘤小鼠模型实验证实，该微小RNA联合疗法可降低氧化应激水平、维持线粒体功能并减轻心脏功能障碍。上述研究结果揭示了一种全新的心脏保护策略，有待在淋巴瘤患者队列中开展进一步的临床验证。 关键词：阿霉素、心脏毒性、淋巴瘤、微小RNA、CombiGEM、心脏保护