B4GALT3 up-regulation by miR-27a contributes to the oncogenic activity in human cervical cancer cells

Cancer Lett. 2016 Jun 1;375(2):284-292. doi: 10.1016/j.canlet.2016.03.016. Epub 2016 Mar 14.

Abstract

β-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for the generation of poly-N-acetyllactosamine and is involved in tumorigenesis. However, B4GALT3-dysregulation and its role in cervical cancer cells are unknown. Herein, we found that B4GALT3 was upregulated in cervical cancer tissues compared to adjacent non-tumor tissues. B4GALT3-overexpression promoted, whereas B4GALT3-knockdown suppressed the cellular migration, invasion and EMT of HeLa and C33A cervical cancer cells. To explore the mechanism of dysregulation, B4GALT3 was predicted to be a target of miR-27a. EGFP and pGL3-promoter reporter assay showed miR-27a binds to B4GALT3 3'UTR region but enhanced its expression. RT-qPCR showed miR-27a was also upregulated and presented positive correlation with B4GALT3-expression in cervical cancer tissues. miR-27a-overexpression promoted, but blocking-miR-27a repressed these malignancies in HeLa and C33A cells. Furthermore, shR-B4GALT3 counteracted the promotion of malignancies induced by miR-27a, suggesting miR-27a upregulates B4GALT3 to enhance tumorigenic activities. In addition, we found that B4GALT3 significantly enhances β1-integrin stability, thus mediating promotion of B4GALT3 on malignancy in cervical cancer cells. Altogether, our findings evidenced that B4GALT3 upregulated by miR-27a contributes to the tumorigenic activities by β1-integrin pathway and might provide potential biomarkers for cervical cancer.

Keywords: B4GALT3; Cervical cancer cells; EMT; miR-27a; β1-integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Female
  • Galactosyltransferases / biosynthesis*
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Integrin beta1 / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Integrin beta1
  • MIRN27 microRNA, human
  • MicroRNAs
  • Galactosyltransferases
  • beta4-galactosyltransferase III