雌激素受体α介导氧化磷酸化通路在肺癌发生中的作用

doi:10.3969/j.issn.1004-616x.2021.04.004

癌变·畸变·突变 ›› 2021, Vol. 33 ›› Issue (4): 262-268.doi: 10.3969/j.issn.1004-616x.2021.04.004

雌激素受体α介导氧化磷酸化通路在肺癌发生中的作用

曾卓颖^1,2, 吴德生⁴, 鲁晶晶³, 廖慧³, 赖洪飘³, 袁建辉³, 胡章立^1,2

1. 深圳大学生命与海洋科学学院, 广东深圳 518060;
2. 深圳大学物理与光电工程学院, 广东深圳 518060;
3. 深圳市南山区疾病预防控制中心, 广东深圳 518054;
4. 深圳市疾病预防控制中心, 广东深圳 518055

收稿日期:2021-05-18 修回日期:2021-06-09 出版日期:2021-07-30 发布日期:2021-07-29
通讯作者: 袁建辉,E-mail:jianhui_yuan@126.com;胡章立,E-mail:huzl@szu.edu.cn E-mail:jianhui_yuan@126.com;huzl@szu.edu.cn
作者简介:曾卓颖,E-mail:zengzhuoying1204@126.com。

Mediation by estrogen receptor α on oxidative phosphorylation pathways in development of lung cancer

ZENG Zhuoying^1,2, WU Desheng⁴, LU Jingjing³, LIAO Hui³, LAI Hongpiao³, YUAN Jianhui³, HU Zhangli^1,2

1. College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060;
2. College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060;
3. Nanshan District Center for Disease Control and Prevention, Shenzhen 518054;
4. Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, Guangdong, China

Received:2021-05-18 Revised:2021-06-09 Online:2021-07-30 Published:2021-07-29

摘要/Abstract

摘要： 目的：通过生物信息学方法探讨雌激素受体α（ESRRA）在肺癌发生发展中的作用。方法：利用UALCAN在线平台对人肺癌组织（包括肺腺癌与肺鳞癌）和癌旁正常肺组织中ESRRA基因的表达变化进行分析，并利用Kaplan-Meier Plotter数据库对肺癌中ESRRA及其相关基因的表达进行生存分析。利用GEPIA2在线平台获得与ESRRA表达模式相似的前50个基因，在GeneMANIA在线平台上构建这50个基因编码的蛋白质-蛋白质的相互作用网络，并通过DAVID数据库对该50个基因群进行GO分析和KEGG通路富集。通过TIMER 2.0在线平台分析肺癌组织中ESRRA与富集在氧化磷酸化通路中核心基因表达水平的相关性。利用Western blot法验证ESRRA蛋白在肺癌细胞系中的表达水平。结果：与癌旁正常肺组织相比，ESRRA在肺癌组织中高表达（P<0.01），ESRRA表达水平高的肺癌患者显示出较差的预后（P<0.01）。与ESRRA表达模式相似的前50个基因主要富集在氧化磷酸化通路，包括ATP5B、ATP5G3、COX5A、COX8A、SDHD、UQCRC1和UQCRC2。其中ATP5B、COX8A和UQCRC1在肺癌组织中的表达水平与ESRRA的表达呈正相关（P<0.05）。ATP5B、ATP5G3、COX5A、COX8A、SDHD、UQCRC1和UQCRC2在肺癌组织中均高表达，ATP5B、ATP5G3、COX5A、COX8A表达水平高和SDHD表达水平低的肺癌患者均显示出较差的预后（P<0.01）。Western blot验证结果显示，与正常人支气管上皮16HBE细胞相比，ESRRA蛋白的相对表达水平在肺腺癌NCI-H1975细胞和肺鳞癌SW900细胞中均高表达（P<0.01）。结论：ESRRA介导氧化磷酸化通路中ATP5B和COX8A的表达改变引起能量代谢紊乱可能是其促进肺癌发生和导致肺癌不良预后的原因之一。

关键词: 雌激素受体α, 生物信息学, 氧化磷酸化通路, 肺腺癌, 肺鳞癌

Abstract: OBJECTIVE: To explore the role of estrogen receptor α (ESRRA) in development of lung cancer using bioinformatics methodology. METHODS: The UALCAN online platform was used to analyze gene expression levels in lung cancer tissues,e.g.,adenocarcinomas and squamous cell carcinomas (LUAD and LUSC) and adjacent normal tissues. The Kaplan-Meier Plotter database was used to perform patients' survival analyses. The GEPIA2 online analysis platform was used to obtain the top 50 genes which had similar expression patterns to that of ESRRA. The protein-protein interaction (PPI) network was constructed using the GeneMANIA online analysis platform. GO analysis and KEGG pathway enrichment were performed for gene clusters in the David database. The TIMER2.0 online analysis platform was used to analyze correlations between ESRRA and gene expression levels which were enriched in oxidative phosphorylation pathways in lung cancer tissues. Expression levels of ESRRA were analyzed using Western blot. RESULTS: Transcription levels of ESRRA in LUAD and LUSC tissues were significantly higher than those in normal lung tissues (P<0.01),and the higher levels of ESRRA were associated with poorer lung cancer prognosis (P<0.01). Expression levels of the top 50 genes which were similar to that of ESRRA were mainly enriched in the oxidative phosphorylation pathways in lung cancer tissues. These genes were mainly:ATP5B,ATP5G3,COX5A,COX8A,SDHD,UQCRC1 and UQCRC2. Moreover,expressions of ATP5B,COX8A and UQCRC1 were positively correlated with that of ESRRA (P<0.05),and that of ATP5B,ATP5G3,COX5A with poorer prognosis (P<0.01). On the other hand, reduced expression levels of SDHD indicate poorer prognosis (P<0.01). Western blotting results indicate that the relative expression of ESRRA in NCI-H1975 cells was higher than that in 16HBE cells (P<0.01),and the relative expression of ESRRA in SW900 cells was higher than that in 16HBE cells (P<0.01). CONCLUSION: ESRRA-mediated changes in the expressions of ATP5B and COX8A in the oxidative phosphorylation pathways which were mainly involved with energy metabolism disorder. Our data suggest that ESRRA contributes to the development and prognosis of lung cancers.

Key words: estrogen receptor α, bioinformatics, oxidative phosphorylation pathway, lung adenocarcinoma, lung squamous cell carcinoma

中图分类号:

R734.2

曾卓颖, 吴德生, 鲁晶晶, 廖慧, 赖洪飘, 袁建辉, 胡章立. 雌激素受体α介导氧化磷酸化通路在肺癌发生中的作用[J]. 癌变·畸变·突变, 2021, 33(4): 262-268.

ZENG Zhuoying, WU Desheng, LU Jingjing, LIAO Hui, LAI Hongpiao, YUAN Jianhui, HU Zhangli. Mediation by estrogen receptor α on oxidative phosphorylation pathways in development of lung cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 262-268.

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雌激素受体α介导氧化磷酸化通路在肺癌发生中的作用

Mediation by estrogen receptor α on oxidative phosphorylation pathways in development of lung cancer

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