FAM64A aggravates proliferation, invasion, lipid droplet formation, and chemoresistance in gastric cancer: A biomarker for aggressiveness and a gene therapy target.

Autor: Yun WJ; Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China., Zhang L; Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China., Yang N; Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China., Cui ZG; Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui, Japan., Jiang HM; Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China., Ha MW; Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China., Yu DY; Department of Cell Biology, Basic Medical College of Chengde Medical University, Chengde, China., Zhao MZ; Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China., Zheng HC; Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China.
Jazyk: angličtina
Zdroj: Drug development research [Drug Dev Res] 2023 Nov; Vol. 84 (7), pp. 1537-1552. Date of Electronic Publication: 2023 Aug 11.
DOI: 10.1002/ddr.22105
Abstrakt: FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.
(© 2023 The Authors. Drug Development Research published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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