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MiR-142-3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer

Tao Xu1, Bang-Shun He1, Bei Pan1

  • 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Journal of Cellular Physiology
|November 2, 2019
PubMed

Insights

MicroRNA-142-3p is decreased in breast cancer (BC). Restoring miR-142-3p suppresses BC growth and metastasis by targeting the RAC1/PAK1 pathway, indicating its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The role of microRNA-142-3p (miR-142-3p) in breast cancer (BC) is not well understood, despite its investigation in other cancers.
  • miR-142-3p expression levels are significantly reduced in both breast cancer cell lines and tumor tissues.

Purpose of the Study:

  • To investigate the function and mechanism of miR-142-3p in breast cancer.
  • To determine if miR-142-3p acts as a tumor suppressor in breast cancer.

Main Methods:

  • Gain-of-function assays were performed in vitro and in vivo to assess the effect of elevated miR-142-3p expression on BC cell lines.
  • Western blotting and phosphorylation assays were used to analyze protein expression and activity.
  • Rescue experiments with RAC1 overexpression were conducted to validate the mechanism.

Main Results:

  • Elevated miR-142-3p expression significantly suppressed the growth and metastasis of breast cancer cells.
  • miR-142-3p was found to regulate ras-related C3 botulinum toxin substrate 1 (RAC1) protein expression.
  • The miR-142-3p/RAC1 axis suppressed epithelial-to-mesenchymal transition (EMT) markers and PAK1 phosphorylation.
  • Overexpression of RAC1 reversed the tumor-suppressive effects of miR-142-3p.

Conclusions:

  • MicroRNA-142-3p functions as a tumor suppressor in breast cancer by targeting the RAC1/PAK1 pathway.
  • miR-142-3p represents a potential therapeutic target for breast cancer treatment.
Keywords:
PAK1RAC1breast cancermiR-142-3p

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