MicroRNA-186 suppresses cell proliferation and metastasis in bladder cancer

Afr Health Sci. 2022 Dec;22(4):56-63. doi: 10.4314/ahs.v22i4.8.

Abstract

Purpose: Bladder cancer (BCa) is a common malignancy in the urinary system. This study aims to explore the role of miR-186 in BCa tumorigenesis.

Methods: The expression of miR-186 and ADAMTS12 in clinical BCa tissues and cell lines was detected. BCa cell lines T24, 5637 and EJ were used to transfect miR-186 mimics or inhibitors. Luciferase reporter gene detection confirmed the correlation between miR-186 and ADAMTS12. MTT method and flow cytometry were used to detect cell viability and apoptosis. Cell migration and invasion ability was detected by transwell assay. The protein level of ADAMTS12, β-catenin, GSK-3β and p-GSK-3β was determined using western blot analysis.

Results: MiR-186 was negatively correlated with the expression of ADAMTS12 in BCa tissues. Further research confirmed that ADAMTS12 is the direct target of miR-186. In addition, overexpression of miR-186 down-regulated the expression of ADAMTS12, inhibiting cell viability and apoptosis, while knockout of miR-186 led to the opposite result. miR-186 also inhibits the phosphorylation of GSK-3 β and β-catenin without changing the total GSK-3β level. Our study shows that miR-186 has a negative regulatory effect on the expression of ADAMTS12 in clinical specimens and in vitro. miR-186 can inhibit the proliferation and invasion of BCa cells.

Conclusions: miR-186 has the potential to be used as a biomarker in the early detection of BCa.

Keywords: ADAMTS12; bladder cancer; metastasis biomarker; miR-186; proliferation.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / pathology
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • MicroRNAs
  • MIRN186 microRNA, human
  • ADAMTS12 protein, human