A tumor-suppressive microRNA, miR-504, inhibits cell proliferation and promotes apoptosis by targeting FOXP1 in human glioma

Cancer Lett. 2016 Apr 28;374(1):1-11. doi: 10.1016/j.canlet.2016.01.051. Epub 2016 Feb 10.

Abstract

MicroRNAs (miRNAs) have been proposed as useful prognostic cancer biomarkers and as potential molecular targets for treating various cancers. Previous findings have indicated that miR-504 is dysregulated and involved in tumorigenesis of several types of cancer. However, the biological role of miR-504 in glioma remains unclear. In this study, we showed that miR-504 expression was markedly decreased in both glioma tissues and cell lines and that miR-504 downregulation significantly correlated with aggressive clinicopathological features and poor prognosis for glioma patients. In addition, miR-504 overexpression inhibited cell proliferation, induced cell cycle arrest, and promoted apoptosis in glioma cell lines. Furthermore, we identified forkhead box protein P1 (FOXP1) as a direct target of miR-504 using microarray analysis and a luciferase assay. Moreover, we demonstrated that miR-504 regulated glioma tumorigenesis by downregulating FOXP1 expression. Our results suggest that miR-504 might function as an important suppressor of glioma tumorigenesis and could serve as a promising candidate for therapeutic applications in glioma treatment.

Keywords: Downregulation; Forkhead box protein P1; Glioma; miR-504; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • HEK293 Cells
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism

Substances

  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • MIRN504 microRNA, human
  • MicroRNAs
  • Repressor Proteins