miR-182 controls cell growth in gastrointestinal stromal tumors by negatively regulating CYLD expression

Oncol Rep. 2018 Dec;40(6):3705-3713. doi: 10.3892/or.2018.6765. Epub 2018 Oct 3.

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor of the digestive tract. MicroRNAs (miRNAs) are short non-coding RNAs, which control gene expression at a post-transcriptional level. Dysregulated miRNAs are involved in various types of human disease, including cancer. In the present study, it was revealed that miRNA-182 (miR-182) expression was significantly upregulated in human GISTs compared with adjacent normal tissues. Overexpression of miR-182 enhanced GIST-T1 cell growth, with increased proliferation and decreased apoptosis. miR-182 upregulation also promoted colony formation and migration of GIST-T1 cells. In addition, cylindromatosis (CYLD) was identified as a direct target of miR-182. Overexpression of miR-182 suppressed CYLD expression and enhanced downstream nuclear factor (NF)-κB activation. It was also determined that the expression of CYLD was downregulated in association with upregulated miR-182 in human GISTs. In conclusion, these results demonstrated that miR-182 promoted GIST cell growth by negatively regulating CYLD expression. These findings indicated that miR-182 antagonist may be a promising therapeutic strategy for the treatment of human GIST.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Deubiquitinating Enzyme CYLD / genetics*
  • Deubiquitinating Enzyme CYLD / metabolism
  • Down-Regulation
  • Female
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • NF-kappa B / metabolism
  • Up-Regulation

Substances

  • MicroRNAs
  • Mirn182 microRNA, human
  • NF-kappa B
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD