PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism
Abstract 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 imm...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-84368-2 |
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| author | Hongyu Chu Yuezhan Shan Chengwei Jiang Yumin Zhong Zijing Liu Xuedong Fang Zhaoying Yang |
| author_facet | Hongyu Chu Yuezhan Shan Chengwei Jiang Yumin Zhong Zijing Liu Xuedong Fang Zhaoying Yang |
| author_sort | Hongyu Chu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2f8cf295833f4457ac4ef749e4fa5dc2 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2f8cf295833f4457ac4ef749e4fa5dc22025-01-05T12:21:01ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-024-84368-2PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolismHongyu Chu0Yuezhan Shan1Chengwei Jiang2Yumin Zhong3Zijing Liu4Xuedong Fang5Zhaoying Yang6Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Pathology, China-Japan Union Hospital, Jilin UniversityDepartment of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Breast Surgery, China-Japan Union Hospital of Jilin UniversityAbstract 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.https://doi.org/10.1038/s41598-024-84368-2Hepatocellular carcinomaProteomicsPrognostic biomarkersTherapeutic targetBioinformatics analysis |
| spellingShingle | Hongyu Chu Yuezhan Shan Chengwei Jiang Yumin Zhong Zijing Liu Xuedong Fang Zhaoying Yang PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism Scientific Reports Hepatocellular carcinoma Proteomics Prognostic biomarkers Therapeutic target Bioinformatics analysis |
| title | PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism |
| title_full | PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism |
| title_fullStr | PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism |
| title_full_unstemmed | PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism |
| title_short | PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism |
| title_sort | pnma1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism |
| topic | Hepatocellular carcinoma Proteomics Prognostic biomarkers Therapeutic target Bioinformatics analysis |
| url | https://doi.org/10.1038/s41598-024-84368-2 |
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