MicroRNA-127 is a tumor suppressor in human esophageal squamous cell carcinoma through the regulation of oncogene FMNL3

Eur J Pharmacol. 2016 Nov 15:791:603-610. doi: 10.1016/j.ejphar.2016.09.025. Epub 2016 Sep 17.

Abstract

In this study, we investigated the expression patterns and functional roles of microRNA 127 (miR-127) and its target gene Formin-Like 3 (FMNL3) in human esophageal squamous cell carcinoma (ESCC). Quantitative RT-PCR (qRT-PCR) was used to compare miR-127 expression between ESCC cell lines and normal esophageal epithelium cell line, as well as paired ESCC tumors and adjacent normal esophageal tissues in 33 patients. We found miR-127 was aberrantly downregulated in both ESCC cell lines and human ESCC tumors. In ESCC cell lines TE-1 and ECA109 cells, lentiviral-induced miR-127 upregulation markedly inhibited cancer proliferation and migration in vitro, and tumorigenicity in vivo. Through dual-luciferase assay and qRT-PCR, FMNL3 was confirmed to be the downstream target gene of miR-127 in ESCC. Finally, FMNL3 was downregulated by siRNA in TE-1 and ECA109 cells. And we discovered that SiRNA-induced FMNL3 downregulation had tumor suppressive effect in ESCC, inhibiting cancer proliferation, migration in vitro, and tumorigenicity in vivo. These results suggest that miR-127 is downregulated and acting as tumor suppressor in ESCC. Inversely, FMNL3, the target gene of miR-127, is upregulated and acting as an oncogene in ESCC.

Keywords: Cancer in vitro growth; Cancer in vivo growth, FMNL3; Esophageal squamous cell carcinoma; MiR-127.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Esophagus / cytology
  • Esophagus / pathology
  • Female
  • Formins
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Oncogenes / genetics*
  • Proteins / genetics*
  • Up-Regulation / genetics

Substances

  • FMNL3 protein, human
  • Formins
  • MIRN127 microRNA, human
  • MicroRNAs
  • Proteins