PNMA1是一种与胆汁酸代谢相关的新型免疫调节剂及肝细胞癌治疗靶点。

PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism.

作者信息

Chu Hongyu, Shan Yuezhan, Jiang Chengwei, Zhong Yumin, Liu Zijing, Fang Xuedong, Yang Zhaoying

机构信息

Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.

Department of Pathology, China-Japan Union Hospital, Jilin University, Changchun, 130033, Jilin, China.

出版信息

Sci Rep. 2025 Jan 3;15(1):738. doi: 10.1038/s41598-024-84368-2.

Hepatocellular carcinoma (HCC) necessitates innovative prognostic biomarkers and therapeutic targets. By investigating PNMA1 in HCC via the TCGA and GEO databases and our clinical data, we found that its overexpression is associated with worse survival. The relevance of PNMA1 extends to immune factors such as M1 macrophages, CD8 T cells, and immune checkpoints. Mechanistically, PNMA1 shapes a suppressive tumor microenvironment strongly linked to bile acid metabolism. It promotes tumor progression via immune inhibition and PI3K-AKT pathway activation. Notably, PNMA1 has emerged as a promising therapeutic target for tyrosine kinase inhibitors, as confirmed by reduced IC50 values and molecular docking. Experimental knockdown of PNMA1 hindered HepG2 cell proliferation and migration. Furthermore, PNMA1 is a pivotal HCC biomarker and therapeutic target with a focus on cancer progression, immune modulation, and bile acid metabolism.

肝细胞癌（HCC）需要创新的预后生物标志物和治疗靶点。通过利用TCGA和GEO数据库以及我们的临床数据对HCC中的PNMA1进行研究，我们发现其过表达与较差的生存率相关。PNMA1的相关性延伸至免疫因子，如M1巨噬细胞、CD8 T细胞和免疫检查点。从机制上讲，PNMA1塑造了一个与胆汁酸代谢密切相关的抑制性肿瘤微环境。它通过免疫抑制和PI3K-AKT途径激活促进肿瘤进展。值得注意的是，PNMA1已成为酪氨酸激酶抑制剂有前景的治疗靶点，IC50值降低和分子对接证实了这一点。实验性敲低PNMA1可阻碍HepG₂细胞增殖和迁移。此外，PNMA1是一个关键的HCC生物标志物和治疗靶点，重点在于癌症进展、免疫调节和胆汁酸代谢。