Department of Anesthesiology, The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, The 1st Affiliated Hospitals of Southern University of Science and Technology, Shenzhen, China.
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.
Cancer Med. 2019 Dec;8(18):7762-7773. doi: 10.1002/cam4.2659. Epub 2019 Oct 30.
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.
COX7A1 是细胞色素 c 氧化酶的一个亚基，在将周边部分整合到线粒体呼吸链中的多亚基异质复合物中的超级组装中发挥重要作用。近年来，一些研究人员已经确定 COX7A1 与人类癌细胞代谢和治疗有关。在这项研究中，我们主要探讨了 COX7A1 对肺癌细胞活力的影响。通过载体转染在 NCI-H838 细胞中诱导 COX7A1 的过表达。在不同组中评估细胞增殖、集落形成和细胞凋亡。此外，通过检测 p62 和 LC3 的表达水平以及串联 mRFP-GFP-LC3 报告基因测定分别分析自噬。我们的结果表明，COX7A1 的过表达抑制了人非小细胞肺癌细胞的增殖和集落形成能力，并促进了细胞凋亡。此外，COX7A1 的过表达通过下调 PGC-1α 和上调 NOX2 阻断自噬通量并导致自噬体的积累。进一步分析表明，COX7A1 过表达对细胞活力的影响部分依赖于自噬的抑制。在此，我们通过影响自噬来确定 COX7A1 在调节肺癌的发生和发展中起着关键作用。尽管 COX7A1、PGC-1α 和 NOX2 之间的串扰需要进一步研究，但我们的研究为 COX7A1 对抗人类非小细胞肺癌的治疗作用提供了新的见解。
