miR-202 Inhibits Cell Proliferation, Migration, and Invasion by Targeting Epidermal Growth Factor Receptor in Human Bladder Cancer

Oncol Res. 2018 Jul 5;26(6):949-957. doi: 10.3727/096504018X15149787144385. Epub 2018 Jan 3.

Abstract

Recent studies have demonstrated that miR-202 is associated with several types of cancer; however, the expression and function of miR-202 have not been investigated in bladder cancer. We analyzed the expression of miR-202 in bladder cancer tissues and adjacent noncancerous tissues. The effect of miR-202 on the proliferation, migration, and invasion was evaluated by in vitro assays. The target gene of miR-202 was assessed by luciferase reporter assay. In this study, miR-202 was found to be significantly downregulated in bladder cancer cell lines and tissues and was highly correlated with the T classification, N classification, grade, and recurrence. Ectopic expression of miR-202 suppressed cell viability, colony formation, cell migration, and invasion in vitro and inhibited xenograft tumor growth in vivo. Inversely, downregulation of miR-202 had contradictory effects. The 3'-untranslated region (3'-UTR) of epidermal growth factor receptor (EGFR) was identified as a direct target of miR-202 using luciferase reporter assays, and knockdown of EGFR enhanced miR-202-inhibited cell proliferation, migration, and invasion. In conclusion, miR-202 suppresses bladder cancer carcinogenesis and progression by targeting EGFR, thereby representing a potential target for miRNA-based therapy for bladder cancer in the future.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN202 microRNA, human
  • MicroRNAs
  • EGFR protein, human
  • ErbB Receptors