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. 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. 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.

中文翻译：

---

核呼吸因子1通过激活LPCAT1-ERK1/2-CREB轴驱动肝细胞癌进展

核呼吸因子1（NRF1）是一种参与多种肿瘤的转录因子，但其在肝细胞癌（HCC）中的作用仍然难以捉摸。本研究旨在探讨 NRF1 在 HCC 进展中的作用并探讨其潜在机制。NRF1在HCC组织和细胞系中过度表达且高度活跃，NRF1的高表达表明HCC患者的预后不良。NRF1在体外和体内促进HCC细胞的增殖、迁移和侵袭。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。NRF1 在 HCC 中过表达，并通过激活 LPCAT1-ERK1/2-CREB ​​轴促进 HCC 进展。NRF1 是 HCC 患者的一个有前途的治疗靶点。