miR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway

Yanyan Chi1, Feng Wang1, Tengfei Zhang1

  • 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Insights

MicroRNA-516a-3p (miR-516a-3p) suppresses breast cancer growth and metastasis by inhibiting Pygopus2 (Pygo2) and the Wnt/β-catenin pathway. Down-regulation of miR-516a-3p and up-regulation of Pygo2 predict poor prognosis in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-516a-3p (miR-516a-3p) is implicated in tumor suppression, but its role in breast cancer is not fully understood.
  • The expression patterns and functional mechanisms of miR-516a-3p in breast cancer require further investigation.

Purpose of the Study:

  • To elucidate the expression, function, and regulatory mechanisms of miR-516a-3p in breast cancer.
  • To investigate the relationship between miR-516a-3p, Pygopus2 (Pygo2), and the Wnt/β-catenin pathway in breast cancer progression.

Main Methods:

  • Quantitative real-time PCR and Western blot analysis to assess gene and protein expression.
  • Dual luciferase reporter assay to confirm direct targeting.
  • Cell proliferation, migration, and invasion assays.
  • Epithelial-mesenchymal transition (EMT) analysis.
  • Xenograft tumor models in mice.

Main Results:

  • miR-516a-3p was significantly down-regulated, while Pygo2 was up-regulated in breast cancer tissues and cells.
  • Low miR-516a-3p or high Pygo2 expression correlated with poor patient prognosis.
  • Pygo2 was identified as a direct target of miR-516a-3p.
  • miR-516a-3p overexpression inhibited breast cancer cell growth, migration, invasion, and EMT, whereas its down-regulation promoted these processes.
  • miR-516a-3p suppressed breast cancer progression by inhibiting Pygo2 and subsequently activating the Wnt/β-catenin pathway.
  • In vivo studies confirmed that miR-516a-3p inhibits tumor growth and EMT via the Pygo2/Wnt signaling pathway.

Conclusions:

  • miR-516a-3p acts as a tumor suppressor in breast cancer by targeting Pygo2 and inhibiting the Wnt/β-catenin pathway.
  • Restoring miR-516a-3p levels may offer a therapeutic strategy for breast cancer treatment.

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