Huang Masha, Sun Jingyi, Jiang Qingqing, Zhao Xin, Huang Hanxue, Lei Mengrong, Jiang Shilong, Yuan Fuqiang, Liu Zhaoqian
Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China; Institute of Clinical Pharmacology, Central South University, Changsha, 410078, PR China; Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
Department of Geriatrics, Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
Cancer Lett. 2025 Mar 1;612:217494. doi: 10.1016/j.canlet.2025.217494. Epub 2025 Jan 23.
Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality. Resistance to platinum-based chemotherapy, such as cisplatin, significantly limits treatment efficacy. Circular RNAs (circRNAs) have emerged as key regulators of cancer progression and chemotherapy resistance due to their stable structure, which protects them from degradation. In this study, we focus on circKIAA0182, a circRNA identified as highly expressed in cisplatin-resistant NSCLC cells through profiling. We explore its role in cell proliferation, migration, invasion, apoptosis, and cisplatin resistance. Our findings show that circKIAA0182 promotes cisplatin resistance and tumor progression in NSCLC, in vitro and in vivo. Furthermore, we discovered that circKIAA0182 may interact with the RNA-binding protein YBX1, potentially mediating its oncogenic and cisplatin-resistant functions. The biological role of circKIAA0182 presents a promising target for developing therapeutic strategies to overcome NSCLC progression and cisplatin resistance.
肺癌,尤其是非小细胞肺癌(NSCLC),仍然是癌症相关死亡的主要原因。对顺铂等铂类化疗药物的耐药性显著限制了治疗效果。环状RNA(circRNA)因其稳定的结构能够保护自身不被降解,已成为癌症进展和化疗耐药性的关键调节因子。在本研究中,我们聚焦于circKIAA0182,这是一种通过基因表达谱分析确定在顺铂耐药的NSCLC细胞中高表达的circRNA。我们探究了它在细胞增殖、迁移、侵袭、凋亡以及顺铂耐药性方面的作用。我们的研究结果表明,circKIAA0182在体外和体内均促进NSCLC的顺铂耐药性和肿瘤进展。此外,我们发现circKIAA0182可能与RNA结合蛋白YBX1相互作用,潜在地介导其致癌和顺铂耐药功能。circKIAA0182的生物学作用为开发克服NSCLC进展和顺铂耐药性的治疗策略提供了一个有前景的靶点。