MiR-22-silenced cyclin a expression in colon and liver cancer cells is regulated by bile acid receptor

Fan Yang, Ying Hu, Hui Xin Liu, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Because of the significant tumor-suppressive role of microRNA-22 (miR-22), the current study was designed to understand the regulation of miR-22 and to identify additional downstream miR-22 targets in liver and colon cells. The data showed that miR-22 was transcriptionally regulated by bile acid receptor farnesoid X receptor (FXR) through direct binding to an invert repeat 1 motif located at -1012 to -1025 bp upstream from miR-22. Among the studied primary and secondary bile acids, chenodeoxycholic acid, which has the highest binding affinity to FXR, induced miR-22 level in both Huh7 liver and HCT116 colon cells in a dose- and time-dependent manner. In addition, cyclin A2 (CCNA2) was identified as a miR-22 novel target in liver and colon cancer cells. The sequence of miR-22, which is conserved in mice, rats, humans, and other mammalians, aligns with the sequence of 3′-UTR of CCNA2. Chenodeoxycholic acid treatment and miR-22 mimics reduced CCNA2 protein and increased the number of G0/G1 Huh7 and HCT116 cells. In FXRKO mice, reduction of miR-22 was accompanied by elevated hepatic and ileal CCNA2 protein, as well as an increased number of hepatic and colonic Ki-67-positive cells. In humans, the expression levels of miR-22 and CCNA2 are inversely correlated in liver and colon cancers. Taken together, our data showed that bile acid-activated FXR stimulates miR-22-silenced CCNA2, a novel pathway for FXR to exert its protective effect in the gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)6507-6515
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number10
DOIs
StatePublished - Mar 6 2015

Fingerprint

Cyclins
Liver Neoplasms
Bile Acids and Salts
MicroRNAs
Liver
Colonic Neoplasms
Cyclin A2
Cells
HCT116 Cells
Chenodeoxycholic Acid
Colon
3' Untranslated Regions
Gastrointestinal Tract
Proteins
Rats
Tumors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

MiR-22-silenced cyclin a expression in colon and liver cancer cells is regulated by bile acid receptor. / Yang, Fan; Hu, Ying; Liu, Hui Xin; Wan, Yu-Jui Yvonne.

In: Journal of Biological Chemistry, Vol. 290, No. 10, 06.03.2015, p. 6507-6515.

Research output: Contribution to journalArticle

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