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MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma
- Source :
- Current Issues in Molecular Biology, Vol 45, Iss 9, Pp 7432-7448 (2023)
- Publication Year :
- 2023
- Publisher :
- MDPI AG, 2023.
-
Abstract
- The prognosis of patients with advanced renal cell carcinoma (RCC) has improved with newer therapies, including molecular-targeted therapies and immuno-oncology agents. Despite these therapeutic advances, many patients with metastatic disease remain uncured. Inhibition of glycogen synthase kinase-3β (GSK-3β) is a promising new therapeutic strategy for RCC; however, the precise regulatory mechanism has not yet been fully elucidated. MicroRNAs (miRNAs) act as post-translational regulators of target genes, and we investigated the potential regulation of miRNAs on GSK-3β in RCC. We selected nine candidate miRNAs from three databases that could potentially regulate GSK-3β. Among these, hsa-miR-4465 (miR-4465) was downregulated in RCC cell lines and renal cancer tissues. Furthermore, luciferase assays revealed that miR-4465 directly interacted with the 3′ untranslated region of GSK-3β, and Western blot analysis showed that overexpression of miR-4465 significantly decreased GSK-3β protein expression. Functional assays showed that miR-4465 overexpression significantly suppressed cell invasion of A498 and Caki-1 cells; however, cell proliferation and migration were suppressed only in Caki-1 and A498 cells, respectively, with no effect on cell cycle and apoptosis. In conclusion, miR-4465 regulates GSK-3β expression but does not consistently affect RCC cell function as a single molecule. Further comprehensive investigation of regulatory networks is required in this field.
Details
- Language :
- English
- ISSN :
- 14673045 and 14673037
- Volume :
- 45
- Issue :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- Current Issues in Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9ac6ea5ad56e4068bf42bd8b1f8af74a
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/cimb45090470