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It accelerates tumor progression through immune inhibition and PI3K–AKT activation, and supports therapeutic relevance for tyrosine kinase inhibitors through IC50 reduction, docking evidence, and PNMA1 knockdown effects on HepG2 proliferation and 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is the relationship between PNMA1 overexpression and hepatocellular carcinoma prognosis?","Question",{"text":63,"@type":64},"PNMA1 overexpression is associated with worse survival in hepatocellular carcinoma, based on analyses using TCGA, GEO, and clinical data.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does PNMA1 influence the tumor immune microenvironment in HCC?",{"text":68,"@type":64},"PNMA1 is linked to immune factors including M1 macrophages, CD8+ T cells, and immune checkpoints, and mechanistically promotes an immunosuppressive tumor microenvironment.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is bile acid metabolism important in the study of PNMA1?",{"text":72,"@type":64},"The study shows that PNMA1 is strongly connected to bile acid metabolism and that this connection relates to how PNMA1 shapes tumor progression and immune suppression.",{"name":74,"@type":61,"acceptedAnswer":75},"What evidence supports PNMA1 as a therapeutic target?",{"text":76,"@type":64},"Therapeutic relevance is supported by reduced IC50 values and molecular docking with tyrosine kinase inhibitors, along with experimental PNMA1 knockdown reducing HepG2 cell proliferation and migration.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},375759,1790444240,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,123,126,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & 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modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism  \nHongyu Chu1, Yuezhan Shan1, Chengwei Jiang3, Yumin Zhong1, Zijing Liu1, Xuedong Fang1􀀍& Zhaoying Yang2􀀍  \nHepatocellular carcinoma (HCC) necessitates innovative prognostic biomarkers and therapeutic targets. By investigating PNMA1 in HCC via theTCGA 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.  \nKeywords Hepatocellular carcinoma, Proteomics, Prognostic biomarkers, Therapeutic target, Bioinformatics analysis  \nHepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer that significantly impacts patients’ quality of life. The rich blood supply of the liver renders it susceptible to progression and metastasis1,2. Unfortunately, the majority of HCC cases are diagnosed at an advanced stage, resulting in a 5-year survival rate of only 5–15%3. Given the bleak prognosis associated with HCC, identifying novel prognostic biomarkers and targeted therapies to increase the well-being of affected individuals is imperative. Emerging evidence suggests a potential link between bile acid metabolism, tumor immunity, and HCC4. Bile acids, which consist of primary and secondary forms, are vital for the digestion and absorption of lipids from the daily diet5. Nevertheless, the precise relationships among bile acid metabolism, tumor immunity, and gene dysregulation remain elusive. Studies6,7 have shown that m6A regulatory factors play an irreplaceable role in the prognosis and immune infiltration of HCC, providing broad research directions for immunotherapeutic targets of HCC. Investigating these potential interconnections8 holds promise in uncovering novel insights for HCC treatment.  \nPNMA Family Member 1 (PNMA1), also known as MA1, belongs to the paraneoplastic Ma family (PNMA), which has more than fifteen members. Previous investigations of PNMA1 have focused primarily on paraneoplastic neurological syndromes9. In mouse neurons, PNMA1 has been identified as a proapoptotic protein10. As demonstrated by Jiang et al. pancreatic ductal adenocarcinoma is characterized by the presence of PNMA1, which plays an oncogenic role through the activation of the MAPK and PI3K/AKT pathways11. Moreover, miR-33a-5p has been found to regulate PNMA1, leading to an increased proliferation rate and enhanced epithelial‒mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway. However, the relationship between PNMA1 and tumor immunity in HCC remains unexplored, necessitating further investigation into the potential mechanisms of PNMA1 .  \nIn addition to elucidating the impact of PNMA1 on HCC progression, this study sought to determine its diagnostic and prognostic relevance. Importantly, we examined the interplay between PNMA1 and tumor immunity, potentially involving bile acid excretion and detoxification. These findings underscore the importance of bile acid metabolism and highlight PNMA1 as a promising novel target for HCC therapy.  \n1Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China. 2Department of Breast Surgery, China-Japan ","cbCaioVJOAL4bXbE","https://ap.wps.com/l/cbCaioVJOAL4bXbE","pdf",8111108,17,"English","# Methods\n## Sources of information on gene and protein expression levels\n## Analysis of differential expression of PNMA1","[{\"question\":\"What is the relationship between PNMA1 overexpression and hepatocellular carcinoma prognosis?\",\"answer\":\"PNMA1 overexpression is associated with worse survival in hepatocellular carcinoma, based on analyses using TCGA, GEO, and clinical data.\"},{\"question\":\"How does PNMA1 influence the tumor immune microenvironment in HCC?\",\"answer\":\"PNMA1 is linked to immune factors including M1 macrophages, CD8+ T cells, and immune checkpoints, and mechanistically promotes an immunosuppressive tumor microenvironment.\"},{\"question\":\"Why is bile acid metabolism important in the study of PNMA1?\",\"answer\":\"The study shows that PNMA1 is strongly connected to bile acid metabolism and that this connection relates to how PNMA1 shapes tumor progression and immune suppression.\"},{\"question\":\"What evidence supports PNMA1 as a therapeutic target?\",\"answer\":\"Therapeutic relevance is supported by reduced IC50 values and molecular docking with tyrosine kinase inhibitors, along with experimental PNMA1 knockdown reducing HepG2 cell proliferation and migration.\"}]","PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism | PDF",1790216045,43]