HNF4G increases cisplatin resistance in lung adenocarcinoma via the MAPK6/Akt pathway

PeerJ

article

Jiaqi Liang¹  Guangyin Zhao¹  Yunyi Bian¹  Guoshu Bi¹  Qihai Sui¹  Huan Zhang¹  Haochun Shi¹  Guangyao Shan¹  Yiwei Huang¹  Zhencong Chen¹  Lin Wang¹  Cheng Zhan¹ 

[1] Department of Thoracic Surgery, Zhongshan Hospital, Fudan University

关键词: Lung adenocarcinoma;    Cisplatin;    HNF4G;    MAPK6;    Transcription factor;   

DOI  :  10.7717/peerj.14996

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundLung adenocarcinoma is one of the most common tumors, and cisplatin is frequently used in treating lung adenocarcinoma patients. This study aimed to look into the roles and mechanisms of HNF4G in cisplatin resistance of lung adenocarcinoma.Materials & MethodsCisplatin resistance and gene expression data of 542 cell lines from the CTRP and CCLE databases were analyzed. HNF4G expression was detected in the lung adenocarcinoma cell lines after treatment with various concentrations of cisplatin. Cisplatin sensitivity curves were detected in cells that overexpressed or knocked down HNF4G. The ChIP-Seq data were then analyzed to identify the targets of HNF4G involved in cisplatin resistance. Expression and phosphorylation of the MAPK6/Akt pathway were detected after HNF4G was overexpressed or knocked down. Finally, ChIP-qPCR and dual-luciferase assays were used to investigate the regulation of HNF4G on MAPK6.ResultsIn cell lines, high expression of HNF4G was significantly positively correlated with cisplatin resistance, and lung adenocarcinoma patients who had high HNF4G expression had a poor prognosis. Cisplatin treatment increased HNF4G expression, and overexpression of HNF4G significantly increased the resistance to cisplatin in A549 and HCC827 cells, whereas knockdown of HNF4G had the opposite effect. HNF4G overexpression increased MAPK6 expression and activated the MAPK6/Akt pathway, while an Akt inhibitor reduced the effects of HNF4G on cisplatin resistance. HNF4G bound to the MAPK6 promoter region, promoting MAPK6 expression, according to ChIP-qPCR and luciferase assays.ConclusionBy binding to the MAPK6 promoter region, HNF4G promotes MAPK6 expression and subsequent Akt phosphorylation, resulting in resistance to cisplatin in lung adenocarcinoma.

【 授权许可】

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