MicroRNA-1297 inhibits prostate cancer cell proliferation and invasion by targeting the AEG-1/Wnt signaling pathway

Biochem Biophys Res Commun. 2016 Nov 11;480(2):208-214. doi: 10.1016/j.bbrc.2016.10.029. Epub 2016 Oct 13.

Abstract

MicroRNAs (miRNAs) have been known to be implicated in tumorigenic programs. miR-1297 has been reported to be dysregulated and involved in cancer progression in many types of human cancers. However, the expression level and the role of miR-1297 in prostate cancer remain unclear. Herein, we aimed to investigate the potential role and molecular mechanism of miR-1297 in prostate cancer progression. We found that miR-1297 was significantly downregulated in human prostate cancer specimens as well as in several prostate cancer cell lines. In addition, functional experiments demonstrated that overexpression of miR-1297 remarkably inhibited prostate cancer cell proliferation and invasion whereas miR-1297 suppression significantly promoted prostate cancer cell proliferation and invasion. Bioinformatics analysis showed that the Astrocyte elevated gene-1 (AEG-1), a well-known oncogene, is a predicted target of miR-1297. Dual-luciferase reporter assay showed that miR-1297 was able to directly target the 3'-untranslated region of AEG-1. In addition, RT-qPCR and Western blot analysis showed that miR-1297 regulated the mRNA and protein expression levels of AEG-1. We also showed that miR-1297 was able to regulate the Wnt signaling pathway. Moreover, rescue assays indicated that AEG-1 contributed to miR-1297-endowed effects on cell proliferation and invasion as well as Wnt signaling pathway. Taken together, these findings suggest that miR-1297 inhibits prostate cancer proliferation and invasion by targeting AEG-1, thereby providing novel insight into understanding the pathogenesis of prostate cancer. Thus, miR-1297 may be a novel potential therapeutic candidate to treat prostate cancer.

Keywords: AEG-1; Prostate cancer; Wnt; miR-1297.

MeSH terms

  • 3' Untranslated Regions
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Membrane Proteins
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA-Binding Proteins
  • Wnt Signaling Pathway / genetics*

Substances

  • 3' Untranslated Regions
  • Cell Adhesion Molecules
  • MIRN1297 microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA-Binding Proteins