MicroRNA-137 is negatively associated with clinical outcome and regulates tumor development through EZH2 in cervical cancer

J Cell Biochem. 2018 Jan;119(1):938-947. doi: 10.1002/jcb.26259. Epub 2017 Oct 4.

Abstract

We intend to evaluate the expression, clinical relevance, and functional role of microRNA-137 (miR-137) in human cervical cancer (CC). MiR-137 expressions were assessed by qPCR in CC cell lines and human CC tumors. The correlation between endogenous miR-137 expression and CC patients' postoperative overall survival was examined statistically. CC cell lines, Ca-Ski, and SiHa cells were transduced with lentivirus to ectopically upregulate endogenous miR-137 expressions. Possible inhibitory effects of miR-137 upregulation on CC in vitro proliferation and migration, as well as in vivo transplantation were evaluated. Targeting of enhancer of zeste homolog 2 (EZH2) gene by miR-137 in CC was assessed by dual-luciferase activity assay and qPCR. In CC cells with upregulated miR-137, EZH2 was overexpressed to assess its direct function in miR-137 mediated CC proliferation and migration. MiR-137 was downregulated in both CC cells and human CC tumors. Downregulation of endogenous miR-137 was significantly correlated with CC patients' short overall survival. In CC cells, miR-137 upregulation is tumor-suppressive by inhibiting proliferation and migration in vitro, and transplantation in vivo. EZH2 was a direct downstream target gene of miR-137 in CC. Forced overexpression of EZH2 in miR-137-upregulated CC cells reversed the tumor-suppression induced by miR-137. MiR-137 is lowly expressed in CC and possibly acting as a negative biomarker for CC patients' clinical outcome. MiR-137 upregulation may suppress CC, very likely by inversely regulating EZH2.

Keywords: EZH2; cervical cancer; miR-137; migration; overall survival; proliferation; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease-Free Survival
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Prognosis
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • MIRN137 microRNA, human
  • MicroRNAs
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein