核呼吸因子 1 通过激活 LPCAT1-ERK1/2-CREB 轴促进肝细胞癌进展。

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

机构信息

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.

Insitute for Genome Sciences, University of Maryland School of Medical, Baltimore, MD, 21201, USA.

出版信息

Biol Direct. 2023 Oct 24;18(1):67. doi: 10.1186/s13062-023-00428-z.

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.

背景

核呼吸因子 1（NRF1）是一种参与多种肿瘤的转录因子，但它在肝细胞癌（HCC）中的作用仍不清楚。本研究旨在探讨 NRF1 在 HCC 进展中的作用，并研究其潜在机制。

结果

NRF1 在 HCC 组织和细胞系中过度表达和过度活跃，NRF1 的高表达表明 HCC 患者的预后不良。NRF1 在体外和体内均促进 HCC 细胞的增殖、迁移和侵袭。在机制上，NRF1 通过反式激活溶血磷脂酰胆碱酰基转移酶 1（LPCAT1）激活 ERK1/2-CREB 信号通路，从而促进 HCC 细胞的细胞周期进程和上皮间质转化（EMT）。同时，LPCAT1 通过激活 ERK1/2-CREB 信号通路上调 NRF1 的表达，形成正反馈环。