Effects of ABHD5 overexpression on invasion, migration and AMPK/mTOR pathway in colon cancer cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHAO Shuaihua ¹ , DONG Weihong ¹ , YANG Jing ¹ , HAN Baowei ²

1. Department of Pathology, Anyang District Hospital of Puyang City, Anyang, Henan 455000, P. R. China;
2. Department of General Surgery, Luoyang Central Hospital, Luoyang, Henan 471699, P. R. China;

Corresponding author：

ZHAO Shuaihua, Email: zsl6910m@163.com

Keywords：

alpha/beta hydrolase domain-containing protein 5; colon cancer; invasion; migration; adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin

DOI：

10.7507/1007-9424.202011010

Video：

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Objective To investigate the effects of overexpression of alpha/beta hydrolase domain-containing protein 5 (ABHD5) on the invasion and migration of human colon cancer cell line HCT116 and the pathway of adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR).Methods The expression of ABHD5 in colon cancer tissues and its relationship with clinicopathological features was analyzed by UALCAN database. HCT116 cells were cultured in vitro and transfected with ABHD5 recombinant plasmid, then they were divided into control group, negative transfection group and ABHD5 transfection group. Real time quantitative PCR (qRT-PCR) was used to detect the expression of ABHD5 mRNA in HCT116 cells. The proliferation of HCT116 cells was detected by CCK-8 method. Transwell assay was used to detect the invasion and migration of HCT116 cells. The expression of matrix metalloprotein 9 (MMP-9), E-cadherin, Snail, and AMPK/mTOR pathway proteins p-AMPK, AMPK, p-mTOR and mTOR were detected by Western blot.Results The results of the UALCAN showed that compared with normal colon tissues, the expression of ABHD5 mRNA in colon cancer tissues was decreased (P<0.05), and which in the adenocarcinoma and the N1 stage was lower than that of the mucinous adenocarcinoma (P<0.05) and N0 stage (P<0.05), respectively. Compared with the control group and the negative transfection group, the expression of ABHD5 mRNA in the ABHD5 transfection group was increased (P<0.05), the proliferation inhibition rate of HCT116 cells in the ABHD5 transfection group was increased (P<0.05), the numbers of migration and invasion cells in the ABHD5 transfection group were decreased (P<0.05), the expressions of MMP-9, Snail, p-mTOR and mTOR were reduced, and the expressions of E-cadherin, p-AMPK and AMPK were increased (P<0.05).Conclusions The overexpression of ABHD5 can inhibit the invasion and migration of colon cancer HCT116 cells, activate AMPK, and inhibit the expression of mTOR. It suggests that ABHD5 may play a role in inhibiting colon cancer by affecting AMPK/mTOR pathway.

Citation： ZHAO Shuaihua, DONG Weihong, YANG Jing, HAN Baowei. Effects of ABHD5 overexpression on invasion, migration and AMPK/mTOR pathway in colon cancer cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(7): 850-855. doi: 10.7507/1007-9424.202011010 Copy

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16.	Shang S, Ji X, Zhang L, et al. Macrophage ABHD5 suppresses NFκB-dependent matrix metalloproteinase expression and cancer metastasis. Cancer Res, 2019, 79(21): 5513-5526.
17.	Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol, 2019, 29(3): 212-226.
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21.	Bu H, Liu D, Zhang G, et al. AMPK/mTOR/ULK1 axis-mediated pathway participates in apoptosis and autophagy induction by oridonin in colon cancer DLD-1 cells. Onco Targets Ther, 2020, 13: 8533-8545.

1. 张健, 赵素平, 王宗艳, 等. 结肠癌组织中 STC1 的表达及其与肿瘤微环境的关系. 中国病理生理杂志, 2019, 35(4): 628-635.
2. Zhu Y, Gu L, Lin X, et al. Dynamic regulation of ME1 phosphorylation and acetylation affects lipid metabolism and colorectal tumorigenesis. Mol Cell, 2020, 77(1): 138-149.
3. Oh M, McBride A, Yun S, et al. BRCA1 and BRCA2 gene mutations and colorectal cancer risk: systematic review and meta-analysis. J Natl Cancer Inst, 2018, 110(11): 1178-1189.
4. 常慧, 张雅萌, 丁选胜. 非小细胞肺癌中脂质代谢的研究进展. 中国药科大学学报, 2020, 51(1): 107-113.
5. Scazzocchio B, Varì R, Silenzi A, et al. Dietary habits affect fatty acid composition of visceral adipose tissue in subjects with colorectal cancer or obesity. Eur J Nutr, 2020, 59(4): 1463-1472.
6. Ou J, Peng Y, Yang W, et al. ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield. Nat Commun, 2019, 10(1): 1078.
7. Zhou Q, Wang F, Zhou K, et al. Oncogenic role of ABHD5 in endometrial cancer. Cancer Manag Res, 2019, 11: 2139-2150.
8. Liang M, Chen X, Wang L, et al. Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression. J Exp Clin Cancer Res, 2020, 39(1): 176.
9. Qu YY, Zhao R, Zhang HL, et al. Inactivation of the AMPK-GATA3-ECHS1 pathway induces fatty acid synthesis that promotes clear cell renal cell carcinoma growth. Cancer Res, 2020, 80(2): 319-333.
10. Magaway C, Kim E, Jacinto E. Targeting mTOR and metabolism in cancer: lessons and innovations. Cells, 2019, 8(12): 1584.
11. Wei Q, Zhang B, Li P, et al. Maslinic Acid inhibits colon tumorigenesis by the AMPK-mTOR signaling pathway. J Agric Food Chem, 2019, 67(15): 4259-4272.
12. Chen F, Wen T, Lv Q, et al. Associations between folate metabolism enzyme polymorphisms and lung cancer: a meta-analysis. Nutr Cancer, 2020, 72(7): 1211-1218.
13. Abbaszadeh Z, Çeşmeli S, Biray Avcı Ç. Crucial players in glycolysis: cancer progress. Gene, 2020, 726: 144158.
14. Snaebjornsson MT, Janaki-Raman S, Schulze A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab, 2020, 31(1): 62-76.
15. Mika A, Pakiet A, Czumaj A, et al. Decreased triacylglycerol content and elevated contents of cell membrane lipids in colorectal cancer tissue: a lipidomic study. J Clin Med, 2020, 9(4): 1095.
16. Shang S, Ji X, Zhang L, et al. Macrophage ABHD5 suppresses NFκB-dependent matrix metalloproteinase expression and cancer metastasis. Cancer Res, 2019, 79(21): 5513-5526.
17. Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol, 2019, 29(3): 212-226.
18. Al Khatib AM, Stepan AE, Margaritescu C, et al. E-cadherin and Snail immunoexpression in colorectal adenocarcinomas. Curr Health Sci J, 2019, 45(2): 204-209.
19. Wu S, Zou MH. AMPK, mitochondrial function, and cardiovascular disease. Int J Mol Sci, 2020, 21(14): 4987.
20. Li Y, Shen J, Cheng CS, et al. Overexpression of pyruvate dehydrogenase phosphatase 1 promotes the progression of pancreatic adenocarcinoma by regulating energy-related AMPK/mTOR signaling. Cell Biosci, 2020, 10: 95.
21. Bu H, Liu D, Zhang G, et al. AMPK/mTOR/ULK1 axis-mediated pathway participates in apoptosis and autophagy induction by oridonin in colon cancer DLD-1 cells. Onco Targets Ther, 2020, 13: 8533-8545.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of ABHD5 overexpression on invasion, migration and AMPK/mTOR pathway in colon cancer cells

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