Protein succinylation involved in the suppression of gastric cancer cell proliferation and migration bybutyric acid
HUANG Yingpeng1, ZHANG Ke2, WU Fangquan2, SHI Dibang3, HAN Qiannian2, WANG Fangyan2.
1.Department of Gastrointestinal Surgery, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; 2.School of Basic Medicine Science, Wenzhou
Medical University, Wenzhou 325035, China; 3.Department of Gastroenterology, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
HUANG Yingpeng,ZHANG Ke,WU Fangquan, et al. Protein succinylation involved in the suppression of gastric cancer cell proliferation and migration bybutyric acid[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(2): 99-105.
Abstract：Objective: To study the effects of butyrate on the proliferation and metabolism of gastric cancer cells, and explore its potential mechanism. Methods: EdU and Transwell were used to detect the proliferation and migration of gastric cancer cells after 5 mmol/L sodium butyrate treatment for 48 h, and the cells were collected and metabolites were extracted for metabolomic analysis. Then we screened out the significantly enriched metabolic pathways and upregulated metabolites. Western blot and cellular immunofluorescence were used to detect the degree of protein succinylation in gastric cancer cells treated with sodium butyrate. Meanwhile, the mRNA level of SIRT5, SUCLG1, SUCLG2, and SUCLA2 was detected by RT-qPCR. Results: After 48 h of sodium butyrate treatment, the proliferation of gastric cancer cells decreased significantly. The metabolic pathways such as “TCA cycle” and “oxidative phosphorylation” were significantly enriched in the treatment group, and the TCA cycle metabolite L-Malic acid, succinyl-CoA and fumarate were significantly upregulated (all P<0.05).Western blot and immunofluorescence showed that the protein succinylation of gastric cancer cells was activated after sodium butyrate treatment (P<0.05). What’s more, RT-qPCR results confirmed that sodium butyrate treatment increased the mRNA expression of succinyl-CoA synthetase encoding gene, including SUCLG1,SUCLG2, and SUCLA2 (all P<0.05), but did not significantly affect the expression of SIRT5 (P<0.05).Conclusion: Butyrate inhibits the proliferation of gastric cancer cells by activating SUCLs expression and increasing the level of succinyl-CoA to further promote the protein succinylation of gastric cancer cells.
