MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer

Biochem Biophys Res Commun. 2015 Apr 10;459(3):515-20. doi: 10.1016/j.bbrc.2015.02.138. Epub 2015 Mar 4.

Abstract

miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer.

Keywords: Human cervical cancer; Tumorigenicity; YOD1; miR-373.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Endopeptidases / genetics*
  • Female
  • Gene Knockdown Techniques
  • HeLa Cells
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Transplantation
  • Oncogenes*
  • Thiolester Hydrolases / antagonists & inhibitors
  • Thiolester Hydrolases / genetics*
  • Tumor Stem Cell Assay
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • MIRN373 microRNA, human
  • MicroRNAs
  • YOD1 protein, human
  • Thiolester Hydrolases
  • Endopeptidases