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The ACSL5 Expression, Prognostic Significance and Its Biological Effecton Gastric Cancer Cell Proliferation

WANG Lejia^1,2#, YUAN Xiaoxia^1,3#, HE Yuyang^1,2, YANG Qiang^1,4, DENG Shihao^1,4, ZHANG Bin^1,2, LUO Yaomin^1,5, LONG Kexun^1,2, YIN Xinqiang^1,3*, XU Chaoying^1,6*, JIANG Zhen^1,2*

(¹Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong 637100, China; ²Department of Biochemistryand Molecular Biology, School of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong 637100, China;³Pathogen Biology Experimental Teaching Center, School of Basic Medicine and Forensic Medicine, North Sichuan Medical College,Nanchong 637000, China; ⁴School of Pharmacy, North Sichuan Medical College, Nanchong 637100, China; ⁵Department of Rehabilitation,Affiliated Hospital of North Sichuan Medical College, Nanchong 637100, China; ⁶Department of Forensic Evidence and Toxicology Analysis,School of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong 637100, China)

Abstract:

ACSL5 (acyl-CoA synthetase long-chain family member 5) can catalyze the formation offatty acyl-CoA from free long-chain fatty acids and CoA, which is a key step in lipid synthesis and fatty acidβ-oxidation. It is reported that ACSL5 is closely related to tumorigenesis, but its expression characteristics andbiological role in gastric cancer are still unclear. Based on iTRAQ quantitative proteomics screening, ACSL5was found to be significantly upregulated in gastric cancer tissues. Combined with GEPIA database analysis,it was further confirmed that ACSL5 was highly expressed in gastric cancer. The expression level of ACSL5 ingastric carcinoma was significantly increased, and it was significantly correlated with the clinicopathological features such as lymph node metastasis and TNM stage. The results of prognostic survival analysis showed that theOS (overall survival) and FP (first progression) of patients with gastric cancer with high ACSL5 expression werepoor, and they were significantly correlated in female, poorly differentiated state, TNM III and TNM IV stages.GSEA gene enrichment analysis showed that 33 pathways were significantly enriched in ACSL5 high expressiongroup, which involved fatty acid metabolism, cholesterol metabolism, lipid production, bile acid metabolism andtricarboxylic acid cycle, respectively. In vitro down-regulation of ACSL5 expression can significantly inhibitthe proliferation of gastric cancer cells and change the levels of TG, TC, LDL-C and HDL-C in cells. This studyshows that ACSL5 is significantly highly expressed in gastric cancer patients and is closely related to the clinicalprognosis of gastric cancer. It may play a cancer-promoting role through multiple intracellular lipid metabolismpathways. Down-regulation of ACSL5 can significantly inhibit the proliferation of gastric cancer cells and reregulate intracellular lipid levels, which provides a research basis for ACSL5 as a potential clinical diagnosis andtreatment target.

CSTR: 32200.14.cjcb.2026.06.0007