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由于HIF-1α-DNMT1轴,NARFL缺乏导致肺癌细胞中的线粒体功能障碍

Hongzhou Liu^1,2,3, Xueqin Wu¹, Tianrong Yang¹

¹School of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, 783# Xindu Avenue, Chengdu, 610500, Sichuan Province, People's Republic of China.

Scientific reports

|October 11, 2023

概括

纳菲尔缺乏会损害非小细胞肺癌 (NSCLC) 细胞中的线粒体功能,通过HIF-1α-DNMT1通路促进药物耐药性和迁移. 这表明纳菲尔是NSCLC预后和治疗的潜在治疗标.

科学领域:

线粒体生物学线粒体生物学
癌症研究癌症研究
分子瘤学分子瘤学

背景情况:

纳菲尔与细胞质铁硫集群组合和肺动脉静脉形形有关.
纳菲尔缺乏会损害线粒体的完整性,并可能恶化肺癌的存活率.
在非小细胞肺癌 (NSCLC) 中纳菲尔缺乏的分子机制尚不清楚.

研究的目的:

调查NSCLC中纳菲尔缺乏症背后的分子机制.
探索纳菲尔在线粒体功能障碍,耐药性和NSCLC细胞迁移中的作用.
评估纳菲尔作为NSCLC的潜在预后和治疗标.

主要方法:

在A549和H1299NSCLC细胞系中进行了纳菲尔敲除.
评估了HIF-1α和DNMT1,线粒体复合体I活性,mtDNA拷贝数和mtND基因表达的蛋白质水平.
进行了细胞增殖,耐药性,迁移和入侵分析.
生存分析使用了患者组织阵列和KM绘图器数据库.

主要成果:

纳菲尔降解剂增加了HIF-1α和DNMT1蛋白水平,同时降低了线粒体复合体I活性,mtDNA拷贝数和ATP水平.
由纳菲尔缺乏引起的线粒体功能障碍被siHIF-1α和DNMT1抑制剂逆转.
纳菲尔抗击剂增强了西斯普拉丁耐药性和细胞迁移,siHIF-1α的作用部分逆转.
患有纳菲尔缺乏症的NSCLC患者的生存率较差.

结论:

纳菲尔缺乏症通过HIF-1α-DNMT1轴扰乱NSCLC细胞中的能量代谢.
这种失调促进化学抵抗,增强细胞迁移,导致预后不佳.
纳菲尔代表了改善NSCLC治疗和患者治疗结果的潜在治疗标.

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