MicroRNA-382 inhibits prostate cancer cell proliferation and metastasis through targeting COUP-TFII

Oncol Rep. 2016 Dec;36(6):3707-3715. doi: 10.3892/or.2016.5141. Epub 2016 Oct 3.

Abstract

MicroRNAs (miRNAs) have emerged as important regulators in cancer that are implicated in regulation of various cellular processes. miR-382 has been proposed as a tumor suppressor by several recent studies. However, the function of miR-382 in prostate cancer remains unknown. In this study, we aimed to investigate the potential function of miR-382 in prostate cancer. We found that miR-382 was significantly decreased in prostate cancer specimens and cancer cell lines. The overexpression of miR-382 in prostate cancer cells markedly inhibited cell proliferation, migration, and invasion. In contrast, miR-382 suppression exhibited an opposite effect. Target analysis predicted that chicken ovalbumin upstream promoter transcription factor II (COUP‑TFII) was a direct target of miR-382. This prediction was experimentally confirmed by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and western blot analysis. Our results further demonstrated that miR-382 inhibited the downstream genes of COUP‑TFII, including Snail and matrix metalloproteinase 2 (MMP2). Moreover, the restoration of COUP‑TFII expression significantly blocked the inhibitory effect of miR-382 on cell proliferation, migration, and invasion, and Snail expression. Taken together, this study suggests that miR-382 inhibits prostate cancer cell proliferation and metastasis through inhibiting COUP‑TFII, representing an important new mechanism for understanding prostate cancer pathogenesis and providing a novel therapeutic candidate target for prostate cancer therapy.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • COUP Transcription Factor II / genetics*
  • COUP Transcription Factor II / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • MicroRNAs / physiology*
  • Neoplasm Metastasis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA Interference*
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism

Substances

  • 3' Untranslated Regions
  • COUP Transcription Factor II
  • MIRN382 microRNA, human
  • MicroRNAs
  • NR2F2 protein, human
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • MMP2 protein, human
  • Matrix Metalloproteinase 2