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Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase

Authors Qiu Z, Deng W, Hong Y, Zhao L, Li M, Guan Y, Su Y, Chen C, Shi Q, Yu J, Wang W

Received 14 October 2020

Accepted for publication 2 February 2021

Published 1 March 2021 Volume 2021:14 Pages 1531—1542

DOI https://doi.org/10.2147/OTT.S282906

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Arseniy Yuzhalin


Zhendong Qiu,* Wenhong Deng,* Yupu Hong, Liang Zhao, Man Li, Yongjun Guan, Yingru Su, Chen Chen, Qiao Shi, Jia Yu, Weixing Wang

Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Weixing Wang; Jia Yu
Department of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, People’s Republic of China
Email [email protected]; [email protected]

Purpose: To research the effects of ATP citrate lyase (ACLY) and Sterol-regulatory element binding protein 1 (SREBP1) on the biology and lipid metabolism of colorectal cancer cells.
Methods: Colorectal cancer cells Caco-2 and Lovo were transfected with ACLY or SREBP1 gene knockdown lentiviruses. Four groups were set: ACLY knockdown, SREBP1 knockdown group, empty vector-transfected (negative control), and untreated cells (blank control). Cell proliferation was measured using CCK-8, colony formation, and EdU labeling assays. Apoptosis was detected using Annexin V-APC/7- AAD and JC-1 assay. Transwell migration and wound healing assays analyzed cell migration and invasion. A triglyceride test kit and oil red O stain assessed cell lipid production. Key factors related to lipid metabolism were detected.
Results: ACLY and SREBP1 promoted cell proliferation at 48 and 120 h, but there was no significant difference in Caco-2 cells at 24 h, at which point the effect of SREBP1 was more important. ACLY’s effect on cell proliferation was more obvious at 120 h. Colony formation assays in Caco-2 showed similar results to the CCK-8 assay at 120 h, but ACLY knockdown had no effect in Lovo cells. EDU assays showed that ACLY or SREBP1 facilitated DNA reproduction in the two cell lines, in which SREBP1 was more significant. Knockdown of the two genes showed significant differences in Lovo cells. However, ALCY knockdown promoted apoptosis to a greater extent than SREBP1 knockdown in Caco-2 cells. In addition, ACLY and SREBP1 enhanced migration, invasion, and lipid production in both cell lines. Knockdown of ACLY or SREBP1 reduced lipid metabolism pathway gene expression in the two cell lines.
Conclusion: Knockdown of ACLY and SREBP1 genes inhibit the proliferation, migration, and invasion of colorectal cancer cells, while promoting their apoptosis. Our results identified potential new targets to treat colorectal cancer via lipid synthesis modulation in cancer cells.

Keywords: ATP-citrate lyase, colorectal cancer, lipid metabolism, sterol-regulatory element binding protein 1

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