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MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma

Masaki Murata1, Vladimir Bilim1,2, Yuko Shirono1

  • 1Department of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Current Issues in Molecular Biology
|September 27, 2023
PubMed

Insights

MicroRNAs regulate glycogen synthase kinase-3β (GSK-3β) in renal cell carcinoma (RCC). While miR-4465 targets GSK-3β, its impact on RCC cell functions is complex, necessitating further research into regulatory networks.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Advanced renal cell carcinoma (RCC) treatment has improved but many patients remain uncured.
  • Glycogen synthase kinase-3β (GSK-3β) inhibition is a potential therapeutic strategy for RCC, but its regulation is not fully understood.
  • MicroRNAs (miRNAs) are key post-translational regulators of gene expression.

Purpose of the Study:

  • To investigate the role of miRNAs in regulating GSK-3β expression in RCC.
  • To identify specific miRNAs that target GSK-3β in renal cancer cells.

Main Methods:

  • Candidate miRNAs targeting GSK-3β were selected from databases.
  • Luciferase assays and Western blot analysis were used to confirm miRNA-target interaction and protein expression changes.
  • Functional assays assessed the impact of miRNA overexpression on RCC cell proliferation, migration, invasion, cell cycle, and apoptosis.

Main Results:

  • hsa-miR-4465 (miR-4465) was found to be downregulated in RCC cell lines and tissues.
  • miR-4465 directly targets the 3' untranslated region of GSK-3β, leading to decreased protein expression.
  • Overexpression of miR-4465 suppressed invasion in A498 and Caki-1 cells, but effects on proliferation and migration were cell-specific, with no impact on cell cycle or apoptosis.

Conclusions:

  • miR-4465 regulates GSK-3β expression in RCC.
  • The functional impact of miR-4465 as a single molecule on RCC cell behavior is not consistent.
  • Further investigation into miRNA regulatory networks is crucial for understanding RCC pathogenesis and developing novel therapies.
Keywords:
GSK-3βcompeting endogenous RNAhsa-miR-4465microRNArenal cell carcinoma

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