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

Abstract

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

CLC Number:

R734.2

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

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