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MiR-186-5p suppresses cell migration, invasion, and epithelial mesenchymal transition in bladder cancer by targeting

Qianjin Zhang1,2, Lin Hao1,3, Zhiyong Shen1,4

  • 1Medical College of Soochow University, Suzhou, Jiangsu, China.

Environmental Toxicology
|July 22, 2021
PubMed

Insights

MicroRNA-186-5p targets Ras-related proteins RAB27A/B to suppress bladder cancer (BCa) progression. This study reveals miR-186-5p as a potential therapeutic agent by inhibiting BCa cell proliferation, migration, invasion, and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Bladder cancer (BCa) is a prevalent malignancy with limited therapeutic options.
  • Ras-related proteins RAB27A and RAB27B (RAB27A/B) are implicated in various cancers, but their role in BCa remains unexplored.
  • Understanding the molecular mechanisms driving BCa is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the function and mechanism of RAB27A/B in bladder cancer development.
  • To identify upstream regulators of RAB27A/B in BCa.
  • To explore the therapeutic potential of targeting the miR-186-5p/RAB27A/B axis in BCa.

Main Methods:

  • Gene expression analysis (RT-qPCR) in BCa tissues and cells.
  • Functional assays including cell counting, wound healing, Transwell invasion, and Western blot to assess the impact of RAB27A/B silencing.
  • Bioinformatics analysis and experimental validation to identify upstream microRNA (miRNA) and confirm direct targeting.
  • In vitro and in vivo experiments to evaluate the effect of miR-186-5p overexpression and rescue experiments.

Main Results:

  • RAB27A/B were highly expressed in BCa tissues and cells, and their silencing suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
  • MicroRNA-186-5p (miR-186-5p) was identified as a direct upstream regulator, targeting RAB27A/B and exhibiting downregulated expression in BCa.
  • miR-186-5p overexpression inhibited BCa progression in vitro and in vivo, while RAB27A/B overexpression rescued these effects, indicating miR-186-5p acts through RAB27A/B.
  • miR-186-5p inactivated the PI3K/MAPK signaling pathway by downregulating RAB27A/B.

Conclusions:

  • miR-186-5p acts as a tumor suppressor in BCa by targeting RAB27A/B.
  • The miR-186-5p/RAB27A/B axis regulates BCa cell proliferation, migration, invasion, EMT, and tumor growth via the PI3K/MAPK pathway.
  • Restoring miR-186-5p levels presents a potential therapeutic strategy for bladder cancer.
Keywords:
PI3K/MAPK signaling pathwayRAB27A/Bbladder cancermiR-186-5p

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