Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma Cells

Mol Ther. 2016 Oct;24(10):1806-1822. doi: 10.1038/mt.2016.103. Epub 2016 Jun 2.

Abstract

Aberrant expression of long noncoding RNAs has recently been reported in tumorigenesis and plays a pivotal role in regulating malignant behavior of cancers. In this study, we confirmed that the long noncoding RNAs human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) was up-regulated in glioma tissues as well as in U87 and U251 cells. Knockdown of HCP5 inhibited the malignant biological behavior of glioma cells by reducing proliferation, migration and invasion, and inducing apoptosis. HCP5 regulated the malignant behavior of glioma cells by binding to microRNA-139, which functions as a tumor suppressor. Moreover, knockdown of HCP5 down-regulated Runt-related transcription factor 1, a direct and functional downstream target of microRNA-139 that is involved in microRNA-139-mediated tumor-suppressive effects in glioma cells. Runt-related transcription factor 1 increased promoter activities and upregulated expression of the oncogenic gene astrocyte elevated gene-1 (AEG-1). Runt-related transcription factor 1 also increased the promoter activities and expression of HCP5, which showed a positive feedback loop in regulating the malignant behavior of glioma cells. In conclusion, this study demonstrated that the HCP5-microRNA-139- Runt-related transcription factor 1 feedback loop plays a pivotal role in regulating the malignant behavior of glioma cells, which may provide a potential therapeutic strategy for treating glioma.

MeSH terms

  • Animals
  • Apoptosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Membrane Proteins
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*
  • RNA-Binding Proteins
  • Up-Regulation

Substances

  • Cell Adhesion Molecules
  • Core Binding Factor Alpha 2 Subunit
  • HCP5 long noncoding RNA, human
  • MIRN139 microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Untranslated
  • RNA-Binding Proteins
  • RUNX1 protein, human