Augmented miR-10b expression associated with depressed expression of its target gene KLF4 involved in gastric carcinoma

Int J Clin Exp Pathol. 2015 May 1;8(5):5071-9. eCollection 2015.

Abstract

Previous studies have revealed several targets of miR-10b, such as syndecan-1, HOXD10, TBX5, and E-cadherin. In this study, we aimed to assess whether Krüppel-like factor 4 (KLF4) is a target gene of miR-10b in gastric cancer (GC). Targeting of KLF4 by miR-10b was confirmed by dual-luciferase reporter assays. The expression levels of miR-10b and KLF4 mRNA in 5 different gastric cancer cell lines and 65 pairs of gastric cancer tissues were detected by Real-time PCR. In addition, KLF4 protein in gastric cancer cell lines and 30 GC tissues was measured by western blotting and immunochemistry, respectively. KLF4 is a direct target gene of miR-10b in GC, and its expression is reduced by miR-10b at both mRNA and protein levels. In addition, the expression level of miR-10b was tendentiously upregulated in GC tissues while the expression levels of KLF4 mRNA and protein were decreased in gastric cancer tissues compared with normal adjacent tissue. There was a dramatically inverse correlation between the expression levels of miR-10b and KLF4 mRNA in GC (r=-0.339, P=0.006). These findings indicate that miR-10b was upregulated in GC and may have a key role in GC pathogenesis and development through the downregulation of its target gene KLF4.

Keywords: KLF4; gastric cancer; miR-10b; target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Binding Sites
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transfection
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MIRN10 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Luciferases