Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis

H-L Li1, S Liang, J-H Cui

  • 1The 2nd Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, China. guangyuhant@126.com.

Abstract

Insights

MicroRNA-214 (miR-214) promotes gastric cancer by downregulating GSK-3β, a key regulator of the Wnt/β-catenin pathway. Inhibiting miR-214 reduces cancer cell proliferation and enhances apoptosis, offering a potential therapeutic strategy.

Area of Science:

  • Molecular oncology
  • Cell biology
  • Cancer research

Background:

  • The Wnt/β-catenin pathway is crucial for cell proliferation and apoptosis.
  • Glycogen synthase kinase-3 beta (GSK-3β) negatively regulates this pathway by degrading β-catenin.
  • Reduced GSK-3β expression and elevated miR-214 have been observed in gastric cancer.

Purpose of the Study:

  • To investigate the regulatory role of miR-214 in gastric cancer cell proliferation and apoptosis.
  • To elucidate the mechanism by which miR-214 influences the Wnt/β-catenin pathway.
  • To explore the potential of targeting miR-214 for gastric cancer therapy.

Main Methods:

  • Analysis of miR-214, GSK-3β, and β-catenin expression in gastric cancer tissues and cell lines.
  • Dual luciferase reporter gene assay to confirm the interaction between miR-214 and GSK-3β.
  • Cell proliferation and apoptosis assays (flow cytometry, EdU staining) following miR-214 inhibition and GSK-3β manipulation.

Main Results:

  • Gastric cancer tissues and cells showed increased miR-214 and β-catenin, with decreased GSK-3β.
  • miR-214 directly targets and downregulates GSK-3β expression.
  • Inhibition of miR-214 led to GSK-3β upregulation, reduced β-catenin and survivin, decreased proliferation, and increased apoptosis in gastric cancer cells.

Conclusions:

  • miR-214 promotes gastric cancer progression by inhibiting GSK-3β and activating the Wnt/β-catenin pathway.
  • Inhibiting miR-214 suppresses gastric cancer cell proliferation and induces apoptosis through GSK-3β upregulation.
  • Targeting miR-214 represents a promising therapeutic approach for gastric cancer.

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