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Exploration of the relationship between ACLY and esophageal cancer based on bioinformatics and related experiments

Published on Aug. 29, 2023Total Views: 1621 timesTotal Downloads: 529 timesDownloadMobile

Author: Meng WANG Yang-Yang ZHANG Jing LIU

Affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Keywords: Esophageal cancer ACLY Bioinformatics Cell proliferation

DOI: 10.12173/j.issn.1004-5511.202211002

Reference: Wang M, Zhang YY, Liu J. Exploration of the relationship between ACLY and esophageal cancer based on bioinformatics and related experiments[J]. Yixue Xinzhi Zazhi, 2023, 33(5): 334-342. DOI: 10.12173/j.issn.1004-5511.202211002. [Article in Chinese]

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Abstract

Objective  This study focuses on ATP citrate lyase (ACLY), takes esophageal cancer cells and online databases as the main research subjects, and further explores the expression of ACLY in esophageal cancer cells and its effects on cell growth and proliferation through bioinformatics analysis and cell biology experiments, in order to provide a new target for clinical diagnosis and treatment of esophageal cancer.

Method  The databases such as TCGA were used to analyze the expression of ACLY in esophageal cancer patients, as well as the expression of ACLY in esophageal cancer patients of different race groups and different clinical stages of esophageal cancer. At the same time, the effects of ACLY changes on the proliferation and cell cycle of esophageal cancer cells were detected by basic cell experiments such as CCK-8 method, EdU staining experiment, plate cloning experiment and flow cytometry.

Results  ACLY is highly expressed in various tumor tissues including esophageal cancer. The expression of ACLY is universal, independent of race and gender, and its expression is related to the staging of esophageal cancer and lymph node metastasis. Further experiments in cell biology confirmed that knocking down ACLY could inhibit the proliferation of esophageal cancer cells and block the cell cycle. Overexpression of ACLY could increase the proliferative capacity of esophageal cancer cells and promote cell cycle progression.

Conclusion  ACLY can affect the proliferation ability of esophageal cancer cells, and ACLY may be a potential target for the treatment and prognosis of esophageal cancer.

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References

1.Rogers JE, Sewastjanow-Silva M, Waters RE, et al. Esophageal cancer: emerging therapeutics[J]. Expert Opin Ther Targets, 2022, 26(2): 107-117. DOI: 10.1080/14728222.2022.2036718.

2.GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019[J]. Lancet, 2020, 396(10258): 1204-1222. DOI: 10.1016/S0140-6736(20)30925-9.

3.Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

4.Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the global burden of disease study 2017[J]. Lancet, 2019, 394(11204): 1145-1158. DOI: 10.1016/S0140-6736(19)30427-1.

5.Feng X, Zhang L, Xu S, et al. ATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: an updated review[J]. Prog Lipid Res, 2020,77: 101006. DOI: 10.1016/j.plipres.2019.101006.

6.Du D, Liu C, Qin M, et al. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma[J]. Acta Pharm Sin B, 2022, 12(2): 558-580. DOI: 10.1016/j.apsb.2021.09.019.

7.Zhang ZG, Zhang HS, Sun HL, et al. KDM5B promotes breast cancer cell proliferation and migration via AMPK-mediated lipid metabolism reprogramming[J]. Exp Cell Res, 2019, 379(2): 182-190. DOI: 10.1016/j.yexcr.2019.04.006.

8.Xin M, Qiao Z, Li J, et al. miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer[J]. Oncotarget, 2016, 7(28): 44252-44265. DOI: 10.18632/oncotarget.10020.

9.Migita T, Narita T, Nomura K, et al. ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer[J]. Cancer Res, 2008, 68(20): 8547-8554. DOI: 10.1158/0008-5472.CAN-08-1235.

10.Wang J, Ye W, Yan X, et al. Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia[J]. J Transl Med, 2019, 17(1): 149. DOI: 10.1186/s12967-019-1884-5.

11.Icard P, Wu Z, Fournel L, et al. ATP citrate lyase: a central metabolic enzyme in cancer[J]. Cancer Lett, 2020, 471: 125-134. DOI: 10.1016/j.canlet.2019.12.010.

12.Wu T, Jun S, Choi EJ, et al. 53BP1-ACLY-SLBP-coordinated activation of replication-dependent histone biogenesis maintains genomic integrity[J]. Nucleic Acids Res, 2022, 50(3): 1465-1483. DOI: 10.1093/nar/gkab1300.

13.Pierce MW, Palmer JL, Keutmann HT, et al. ATP-citrate lyase. Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase[J]. J Biol Chem, 1981, 256(17): 8867-8870. DOI: 10.1016/S0167-6911(81)80039-4.

14.Wei X, Shi J, Lin Q, et al. Targeting ACLY attenuates tumor growth and acquired cisplatin resistance in ovarian cancer by inhibiting the PI3K-AKT pathway and activating the AMPK-ROS pathway[J]. Front Oncol, 2021, 11: 642229. DOI: 10.3389/fonc.2021.642229.

15.Csanadi A, Kayser C, Donauer M, et al. Prognostic value of malic enzyme and ATP-citrate lyase in non-small cell lung cancer of the young and the elderly[J]. PLoS One, 2015, 10(5): e0126357. DOI: 10.1371/journal.pone.0126357.

16.Velez BC, Petrella CP, DiSalvo KH, et al. Combined inhibition of ACLY and CDK4/6 reduces cancer cell growth and invasion[J]. Oncol Rep, 2023, 49(2): 32. DOI: 10.3892/or.2022.8469.

17.Khwairakpam AD, Shyamananda MS, Sailo BL, et al. ATP citrate lyase (ACLY): a promising target for cancer prevention and treatment[J]. Curr Drug Targets, 2015, 16(2): 156-163. DOI: 10.2174/1389450115666141224125117.

18.Huang SS, Tsai CH, Kuo CY, et al. ACLY inhibitors induce apoptosis and potentiate cytotoxic effects of sorafenib in thyroid cancer cells[J]. Endocrine, 2022, 78(1): 85-94. DOI: 10.1007/s12020-022-03124-6.

19.Zhang M, Peng R, Wang H, et al. Nanog mediated by FAO/ACLY signaling induces cellular dormancy in colorectal cancer cells[J]. Cell Death Dis, 2022, 13(2): 159. DOI: 10.1038/s41419-022-04606-1.

20.Shah S, Carriveau WJ, Li J, et al. Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism[J]. Oncotarget, 2016, 7(28): 43713-43730. DOI: 10.18632/oncotarget.9666.