CR6-interacting factor 1 inhibits invasiveness by suppressing TGF-β-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

ABSTRACT: CR6-interacting factor 1 (CRIF1) regulates cell cycle progression and the DNA damage response. Here, we show that CRIF1 expression is decreased in hepatocellular carcinoma (HCC) tissues and positively correlates with patients' survival. In vitro, down-regulation of CRIF1 promotes HCC cell proliferation and invasiveness, while over-expression has the opposite effect. in vivo, CRIF1 knockdown enhances growth of HCC xenografts. Analysis of mRNA microarrays showed that CRIF1 knockdown activates genes involved in TGF-β RI/Smad2/3 signaling, leading to epithelial-mesenchymal transition (EMT) and increased matrix metalloproteinase-3 (MMP3) expression. However, cell invasion and EMT are abrogated in HCC cells treated with SB525334, a specific TGF-β RI inhibitor, which indicates the i

SUBMITTER: Zhuang R 

PROVIDER: S-EPMC5706910 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature