{"title":"Vesicle-mediated transport-related gene SEC23A promotes cell proliferation by regulating cell cycle leading to gastric cancer progression.","authors":"Kang Wang, Shihao Rao, Xujin Wei, Wen Xie, Zhijun Hong, Jia Cheng, Xin Chen, Jingjing Hou, Huiqin Zhuo","doi":"10.3724/abbs.2025051","DOIUrl":null,"url":null,"abstract":"<p><p>Gastric cancer (GC) is a highly prevalent and lethal gastrointestinal cancer. Dysregulation of vesicle-mediated transport-related genes (VMTRGs) is closely associated with tumorigenesis and disease progression. However, the prognostic value of VMTRGs in GC remains unclear. In this study, on the basis of our proteomics data and public databases, we identify differentially expressed VMTRGs in infiltrative-type GC with more metastases and recurrences identified by Ming's classification. Least absolute shrinkage and selection operator (LASSO) regression identifies 3 VMTRGs ( <i>SEC23A</i>, <i>RAB31</i>, and <i>GABARAPL2</i>) from 41 infiltrative-associated VMTRGs, based on which a risk model Vesicle-Infiltrative Lasso System (VILS) is constructed, and its effectiveness and potential importance are validated by immune microenvironment analysis and functional enrichment analysis. As an independent prognostic factor for GC, VILS, combined with other clinically independent prognostic factors to form a nomogram, is effective in predicting GC prognosis. The VILS high-risk group has higher M2 macrophage and cancer-associated fibroblast infiltration, and lower infiltration of Th1 cells and natural killer cells. SEC23A is highly expressed in GC tissues and cells. The importance of SEC23A in GC cells is evaluated by <i>in vitro</i> assays including colony formation assay and CCK-8 assay, and by <i>in vivo</i> assay using a subcutaneous xenograft mouse model. The results show that SEC23A promotes GC cell proliferation and tumor growth through regulation of the cell cycle <i>in vitro</i> and <i>in vivo</i>. VILS provides excellent prognostic prediction for GC patients and is correlated with antitumor immune cell infiltration. <i>SEC23A</i>, the dominant gene of VILS, is highly expressed in GC and promotes GC growth and malignant progression through various molecular mechanisms. Our study reveals the effect of SEC23A on the proliferation of gastric cancer cells for the first time. Therefore, SEC23A has the potential to be a new therapeutic target for the diagnosis and treatment of GC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta biochimica et biophysica Sinica","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3724/abbs.2025051","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Gastric cancer (GC) is a highly prevalent and lethal gastrointestinal cancer. Dysregulation of vesicle-mediated transport-related genes (VMTRGs) is closely associated with tumorigenesis and disease progression. However, the prognostic value of VMTRGs in GC remains unclear. In this study, on the basis of our proteomics data and public databases, we identify differentially expressed VMTRGs in infiltrative-type GC with more metastases and recurrences identified by Ming's classification. Least absolute shrinkage and selection operator (LASSO) regression identifies 3 VMTRGs ( SEC23A, RAB31, and GABARAPL2) from 41 infiltrative-associated VMTRGs, based on which a risk model Vesicle-Infiltrative Lasso System (VILS) is constructed, and its effectiveness and potential importance are validated by immune microenvironment analysis and functional enrichment analysis. As an independent prognostic factor for GC, VILS, combined with other clinically independent prognostic factors to form a nomogram, is effective in predicting GC prognosis. The VILS high-risk group has higher M2 macrophage and cancer-associated fibroblast infiltration, and lower infiltration of Th1 cells and natural killer cells. SEC23A is highly expressed in GC tissues and cells. The importance of SEC23A in GC cells is evaluated by in vitro assays including colony formation assay and CCK-8 assay, and by in vivo assay using a subcutaneous xenograft mouse model. The results show that SEC23A promotes GC cell proliferation and tumor growth through regulation of the cell cycle in vitro and in vivo. VILS provides excellent prognostic prediction for GC patients and is correlated with antitumor immune cell infiltration. SEC23A, the dominant gene of VILS, is highly expressed in GC and promotes GC growth and malignant progression through various molecular mechanisms. Our study reveals the effect of SEC23A on the proliferation of gastric cancer cells for the first time. Therefore, SEC23A has the potential to be a new therapeutic target for the diagnosis and treatment of GC.
期刊介绍:
Acta Biochimica et Biophysica Sinica (ABBS) is an internationally peer-reviewed journal sponsored by the Shanghai Institute of Biochemistry and Cell Biology (CAS). ABBS aims to publish original research articles and review articles in diverse fields of biochemical research including Protein Science, Nucleic Acids, Molecular Biology, Cell Biology, Biophysics, Immunology, and Signal Transduction, etc.