XIST promotes gastric cancer (GC) progression through TGF-β1 via targeting miR-185

J Cell Biochem. 2018 Mar;119(3):2787-2796. doi: 10.1002/jcb.26447. Epub 2017 Dec 4.

Abstract

LncRNAs and microRNAs can play significant roles in various cancers, including gastric cancer (GC). In our study, we investigated the role of lncRNA XIST in GC. We observed that XIST was increased in MGC803 and BGC823 cells compared to human normal gastric epithelial GES-1 cells. It was also shown that miR-185 was decreased in GC cell lines. Silencing XIST can inhibit the growth of GC cells and bioinformatics analysis was performed to confirm the correlation between XIST and miR-185. Interestingly, a negative correlation was indicated between XIST and miR-185 in GC cells. In addition, TGF-β1 was predicted as a target gene of miR-185. miR-185 can modulate TGF-β1 expression negatively in vitro. Moreover, we found that sh-XIST inhibited GC development via decreasing TGF-β1 by upregulating miR-185 in vitro. Therefore, we speculated that XIST can act as a competing endogenous lncRNA (ceRNA) to regulate TGF-β1 by sponging miR-185 in GC. Taken these together, it was indicated that XIST/miR-185/TGF-β1 axis participated in the development of GC. XIST could act as a potential prognostic biomarker in GC development.

Keywords: GC; TGF-β1; XIST; miR-185.

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transforming Growth Factor beta1 / biosynthesis*
  • Transforming Growth Factor beta1 / genetics
  • Up-Regulation*

Substances

  • MIRN185 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • XIST non-coding RNA