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

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

  • Biol Direct. 2023 Oct 24;18(1):67. doi: 10.1186/s13062-023-00428-z.
Ran Liu # 1,  Chuanzheng Yin # 1,  Peng Zhao # 1,  Bing Guo 2,  Wenbo Ke 1,  Xichuan Zheng 1,  Dawei Xie 3,  Yaofeng Wang 1,  Gengqiao Wang 1,  Yinzhao Jia 1,  Yang Gao 1,  Wenjun Hu 4,  Gang Logan Liu 4,  Zifang Song 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • 2 Insitute for Genome Sciences, University of Maryland School of Medical, Baltimore, MD, 21201, USA.
  • 3 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, Beijing, 100021, China.
  • 4 School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.
  • 5 Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China. zsong@hust.edu.cn.
  • # Contributed equally.
PMID: 37875967 DOI: 10.1186/s13062-023-00428-z
Abstract

Background: Nuclear 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.

Results: NRF1 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.

Conclusions: NRF1 is overexpressed in HCC and promotes HCC progression by activating LPCAT1-ERK1/2-CREB axis. NRF1 is a promising therapeutic target for HCC patients.

Keywords

Hepatocellular carcinoma; LPCAT1; NRF1; Positive feedback loop; Progression.

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