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M6A连接的ceRNA网络对非小细胞肺癌顺铂敏感性的表观遗传调控

Epigenetic modulation of cisplatin sensitivity by the M6A-linked ceRNA network in non-small cell lung cancer.

作者信息

Wang Qi, Yan He, Zhang Jing, Zhang Jie, Su Xiaomin, Su Zhenzhong

机构信息

Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, People's Republic of China.

Department of General Gynecology, The First Hospital of Jilin University, Changchun, People's Republic of China.

出版信息

Am J Physiol Cell Physiol. 2025 Aug 1;329(2):C481-C499. doi: 10.1152/ajpcell.00881.2024. Epub 2025 Apr 28.

Abstract

Cisplatin resistance significantly impedes effective treatment of non-small cell lung cancer (NSCLC). This study investigates the role of the N6-methyladenosine (M6A)-related circFUT8/miR-185-5p/HNRNPC competing endogenous RNA (ceRNA) axis in NSCLC cisplatin resistance. Bioinformatics analysis identified HNRNPC, a critical M6A modification-related gene, as a promoter of NSCLC proliferation and metastasis. Our in vitro and in vivo experiments reveal that circFUT8 upregulates HNRNPC by sponging miR-185-5p, thus enhancing NSCLC cell proliferation, migration, and invasion while reducing apoptosis and sensitivity to cisplatin. These findings highlight the circFUT8/miR-185-5p/HNRNPC axis as a potential target to overcome chemoresistance in NSCLC. This study identifies the N6-methyladenosine (M6A)-linked circFUT8/miR-185-5p/HNRNPC competing endogenous RNA (ceRNA) network as a key regulator of cisplatin resistance in non-small cell lung cancer (NSCLC). By revealing how circFUT8 modulates HNRNPC through miR-185-5p, this work provides insights into the molecular mechanisms of chemoresistance. The findings suggest potential therapeutic strategies targeting the circFUT8/miR-185-5p/HNRNPC axis to overcome cisplatin resistance in NSCLC, opening new avenues for improved treatment outcomes.

摘要

顺铂耐药显著阻碍了非小细胞肺癌(NSCLC)的有效治疗。本研究调查了N6-甲基腺苷(m6A)相关的circFUT8/miR-185-5p/HNRNPC竞争性内源RNA(ceRNA)轴在NSCLC顺铂耐药中的作用。生物信息学分析确定HNRNPC是一个与m6A修饰相关的关键基因,是NSCLC增殖和转移的促进因子。我们的体外和体内实验表明,circFUT8通过海绵吸附miR-185-5p上调HNRNPC,从而增强NSCLC细胞的增殖、迁移和侵袭,同时减少细胞凋亡和顺铂敏感性。这些发现突出了circFUT8/miR-185-5p/HNRNPC轴作为克服NSCLC化疗耐药的潜在靶点。本研究确定了N6-甲基腺苷(m6A)连接的circFUT8/miR-185-5p/HNRNPC竞争性内源RNA(ceRNA)网络是非小细胞肺癌(NSCLC)顺铂耐药的关键调节因子。通过揭示circFUT8如何通过miR-185-5p调节HNRNPC,这项工作为化疗耐药的分子机制提供了见解。研究结果表明,针对circFUT8/miR-185-5p/HNRNPC轴的潜在治疗策略可克服NSCLC的顺铂耐药,为改善治疗结果开辟了新途径。

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