Nuclear respiratory factor 1 drives hepatocellular carcinoma progression by activating LPCAT1-ERK1/2-CREB axis

Biology Direct

Research

Wenbo Ke¹  Zifang Song¹  Gengqiao Wang¹  Yaofeng Wang¹  Xichuan Zheng¹  Yinzhao Jia¹  Yang Gao¹  Peng Zhao¹  Ran Liu¹  Chuanzheng Yin¹  Bing Guo²  Wenjun Hu³  Gang Logan Liu³  Dawei Xie⁴ 

[1] Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei, China;Insitute for Genome Sciences, University of Maryland School of Medical, 21201, Baltimore, MD, USA;School of Life Science and Technology, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China;State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China;

关键词: NRF1;    LPCAT1;    Hepatocellular carcinoma;    Progression;    Positive feedback loop;   

DOI  :  10.1186/s13062-023-00428-z

 received in 2023-09-12, accepted in 2023-10-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNuclear respiratory factor 1 (NRF1) is a transcription factor that participates in several kinds of tumor, but its role in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the role of NRF1 in HCC progression and investigate the underlying mechanisms.ResultsNRF1 was overexpressed and hyperactive in HCC tissue and cell lines and high expression of NRF1 indicated unfavorable prognosis of HCC patients. NRF1 promoted proliferation, migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NRF1 activated ERK1/2-CREB signaling pathway by transactivating lysophosphatidylcholine acyltransferase 1 (LPCAT1), thus promoting cell cycle progression and epithelial mesenchymal transition (EMT) of HCC cells. Meanwhile, LPCAT1 upregulated the expression of NRF1 by activating ERK1/2-CREB signaling pathway, forming a positive feedback loop.ConclusionsNRF1 is overexpressed in HCC and promotes HCC progression by activating LPCAT1-ERK1/2-CREB axis. NRF1 is a promising therapeutic target for HCC patients.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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Fig. 1: The conceptual framework for adherence to treatment guidelines in private drug outlets in Kisumu, Kenya

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