MiR-198 represses tumor growth and metastasis in colorectal cancer by targeting fucosyl transferase 8

Sci Rep. 2014 Sep 1:4:6145. doi: 10.1038/srep06145.

Abstract

In this study we investigated the biological role and mechanism of miR-198 in colorectal carcinoma (CRC). MiR-198 expression was shown to exhibit a strongly negative correlation with lymph node invasion, distant metastasis and patient survival in examinations of colorectal cancer tissues and paired normal colorectal mucosa tissues. fucosyl transferase 8 (FUT8) was identified as a potential target of miR-198 in bioinformatics analysis and luciferase reporter assays. Overexpression of miR-198 in CRC cell lines decreased FUT8 levels as shown by immunofluorescence analysis, and inhibited cell proliferation, migration, and invasion. These anti-tumor phenotypes were rescued by reconstitution of FUT8 expression. Furthermore, miR-198 was shown to target the 3'UTR of FUT8 directly to downregulate FUT8 expression at both mRNA and protein levels in qRT-PCR and Western blot analyses, respectively. In vivo, restoration of miR-198 significantly inhibited xenograft growth and invasion of CRC tumors in nude mice. Therefore, it could be concluded that miR-198 suppresses the proliferation and invasion of CRC by directly targeting FUT8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Down-Regulation / genetics
  • Fucosyltransferases / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology

Substances

  • 3' Untranslated Regions
  • MIRN198 microRNA, human
  • MicroRNAs
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase