Regulation of UHRF1 by microRNA-378 modulates medulloblastoma cell proliferation and apoptosis

Oncol Rep. 2017 Nov;38(5):3078-3084. doi: 10.3892/or.2017.5939. Epub 2017 Sep 4.

Abstract

A previous study revealed that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) promoted cell proliferation and was a potential biomarker in medulloblastoma (MB). In the present study, we reported that miR-378 inhibited the expression of UHRF1 to affect the proliferation of MB through competitive binding to the same region of its 3'-UTR. We found that the expression of miR-378 was significantly downregulated in MB tissues and inversely correlated with the expression of UHRF1. Western blot analysis revealed that overexpression of miR-378 led to the suppression of UHRF1. Moreover, a dual-luciferase assay demonstrated that miR-378 negatively regulated the activity of target gene UHRF1 by binding to its 3'-UTR. An in vitro assay revealed that overexpression of miR-378 suppressed MB cell proliferation and promoted cell apoptosis. Ectopic expression of UHRF1 rescued miR-378-suppressed cell proliferation and miR-378-promoted cell apoptosis. Collectively, the present study demonstrated that miR-378 could inhibit the proliferation of MB by downregulation of UHRF1 and act as a potential therapeutic target against MB.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism
  • MicroRNAs / genetics*
  • Ubiquitin-Protein Ligases

Substances

  • 3' Untranslated Regions
  • CCAAT-Enhancer-Binding Proteins
  • MIRN378 microRNA, human
  • MicroRNAs
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases