MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
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| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/45/9/470 |
| Summary: | 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. |
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| ISSN: | 1467-3037 1467-3045 |