Tumor-Suppressive Function of miR-30d-5p in Prostate Cancer Cell Proliferation and Migration by Targeting NT5E

Cancer Biother Radiopharm. 2018 Jun;33(5):203-211. doi: 10.1089/cbr.2018.2457.

Abstract

MiR-30d-5p, a member of the microRNA family, was recently reported to regulate androgen receptor signaling in prostate cancer (PCa). Ecto-5'-nucleotidase (NT5E/CD73) is a pivotal regulator of tumor migration and has angiogenetic properties. However, the undiscovered function of miR-30d-5p and whether it targeted NT5E in PCa remain uncertain. In this study, the authors observed miR-30d-5p was significantly downregulated in PCa tissues and cell lines compared with the adjacent normal tissues and normal prostate cells, respectively. The lower expression of miR-30d-5p was found to be inversely correlated with the NT5E expression in PCa tissues. Subsequently, the biological function of miR-30d-5p was evaluated in PCa in vitro. The results indicated that miR-30d-5p overexpression inhibited PCa cell growth and invasion by MTT, Transwell assays, respectively, as well as induced cell cycle G0/G1 phase arrest and apoptosis using flow cytometry analysis. In addition, miR-30d-5p directly bound to the 3'UTR (3' untranslated region) of NT5E in DU-145 and PC-3 cells by luciferase reporter assay. Furthermore, enforced NT5E expression alleviated miR-30d-5p inhibition of PCa cell growth and invasion in DU145 cells. Taken together, these data indicated that miR-30d-5p may be a potential therapeutic target for the treatment of PCa by serving as a tumor suppressor, by negatively regulating NT5E.

Keywords: NT5E; miR-30d-5p; migration; proliferation; prostate cancer.

MeSH terms

  • 5'-Nucleotidase / genetics
  • 5'-Nucleotidase / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation*
  • Follow-Up Studies
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • MIRN30b microRNA, human
  • MicroRNAs
  • 5'-Nucleotidase
  • NT5E protein, human