COX7A1 suppresses the viability of human non-small cell lung cancer cells via regulating autophagy
COX7A1 suppresses the viability of human non-small cell lung cancer cells via regulating autophagy
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COX7A1通过调节自噬抑制人非小细胞肺癌细胞的活力
DOI：
10.1002/cam4.2659
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发表时间：
2019
期刊：
影响因子：
4
通讯作者：
Liu Pengfei
中科院分区：
文献类型：
--
作者：
Zhao Lei;Chen Xin;Feng Yetong;Wang Guangsuo;Nawaz Imran;Hu Lifu;Liu Pengfei
COX7A1是细胞色素c氧化酶的一个亚基，在线粒体呼吸链外周整合成多单位异质复合物的超组装中起重要作用。近年来，一些研究人员发现，COX7A1与人类癌细胞的代谢和治疗有关。在本研究中，我们主要探讨了COX7A1对肺癌细胞活力的影响。载体转染NCI‐H838细胞诱导cox - 7a1过表达。观察各组细胞增殖、集落形成及细胞凋亡情况。此外，通过检测p62和LC3的表达水平，以及mRFP‐GFP‐LC3报告基因串联试验，分析自噬情况。结果表明，过表达COX7A1可抑制人非小细胞肺癌细胞的增殖和集落形成能力，促进细胞凋亡。此外，COX7A1的过表达通过下调PGC‐1α和上调NOX2来阻断自噬通量，导致自噬体的积累。进一步分析表明，COX7A1过表达对细胞活力的影响部分依赖于对自噬的抑制。本研究发现，COX7A1通过影响自噬，在调节肺癌的发生发展中起着关键作用。虽然COX7A1、PGC‐1α和NOX2之间的相互作用还需要进一步研究，但我们的研究为COX7A1治疗人类非小细胞肺癌提供了新的视角。
COX7A1 is a subunit of cytochrome c oxidase, and plays an important role in the super‐assembly that integrates peripherally into multi‐unit heteromeric complexes in the mitochondrial respiratory chain. In recent years, some researchers have identified that COX7A1 is implicated in human cancer cell metabolism and therapy. In this study, we mainly explored the effect of COX7A1 on the cell viability of lung cancer cells. COX7A1 overexpression was induced by vector transfection in NCI‐H838 cells. Cell proliferation, colony formation and cell apoptosis were evaluated in different groups. In addition, autophagy was analyzed by detecting the expression level of p62 and LC3, as well as the tandem mRFP‐GFP‐LC3 reporter assay respectively. Our results indicated that the overexpression of COX7A1 suppressed cell proliferation and colony formation ability, and promoted cell apoptosis in human non‐small cell lung cancer cells. Besides, the overexpression of COX7A1 blocked autophagic flux and resulted in the accumulation of autophagosome via downregulation of PGC‐1α and upregulation of NOX2. Further analysis showed that the effect of COX7A1 overexpression on cell viability was partly dependent of the inhibition of autophagy. Herein, we identified that COX7A1 holds a key position in regulating the development and progression of lung cancer by affecting autophagy. Although the crosstalk among COX7A1, PGC‐1α and NOX2 needs further investigation, our study provides a novel insight into the therapeutic action of COX7A1 against human non‐small cell lung cancer.