CYP27A1 inhibits bladder cancer cells proliferation by regulating cholesterol homeostasis. Issue 1 (2nd January 2019)

• Record Type: Journal Article
• Authors: Liang, Zhijuan; Chen, Yuanbin; Wang, Liping; Li, Dan; Yang, Xuecheng; Ma, Guofeng; Wang, Yonghua; Li, Yongxin; Zhao, Han; Liang, Ye; Niu, Haitao
• Is Part Of: Cell cycle. Volume 18:Issue 1(2019)
• Page Start: 34
• Page End: 45
• Publication Date: 2019-01-02
• Subjects: CYP27A1 -- 27-hydroxycholesterol -- bladder cancer -- ATP-binding cassette transporters -- low-density lipoprotein receptor; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2018.1558868
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: CYP27A1, an enzyme involved in regulating cellular cholesterol homeostasis, converts cholesterol into 27-hydroxycholesterol (27-HC). The relationship between CYP27A1 and cell proliferation was studied to determine the role of CYP27A1 in bladder cancer. The expression of CYP27A1 in three bladder cancer cell lines (T24, UM-UC-3 and 5637) were assessed by qRT-PCR and Western blotting, and cells with stable CYP27A1 expression were generated by lentiviral infection. Cell proliferation was detected by MTT assays, colony formation assays and a tumor xenograft model in vitro and in vivo, and the intracellular 27-HC and cholesterol secretion levels were detected by enzyme-linked immunosorbent assays (ELISA). The results revealed that CYP27A1 expression was downregulated in androgen receptor (AR)-positive T24/UM-UC-3 cells compared with AR-negative 5637 cell. After CYP27A1 expression was restored, cell proliferation was inhibited in vitro and in vivo because much more intracellular 27-HC was produced in the CYP27A1-overexpressing cells than in the control cells. Both T24 and UM-UC-3 cells treated with 27-HC showed similar results. In addition, CYP27A1/27HC could reduce the cellular cholesterol level in both T24 and UM-UC-3 cells by upregulating ATP-binding cassette transporters G1 and A1 (ABCG1 and ABCA1) through Liver X receptors (LXRs) pathway and downregulating low-density lipoprotein receptor (LDLR) expression. These findings all suggest that CYP27A1 is a critical cholesterol sensor in bladder cancer cells that may contribute significantly to bladder cancer proliferation.