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...
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MDPI AG
2023-09-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/9/470 |
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| author | Masaki Murata Vladimir Bilim Yuko Shirono Akira Kazama Kaede Hiruma Masayuki Tasaki Yoshihiko Tomita |
| author_facet | Masaki Murata Vladimir Bilim Yuko Shirono Akira Kazama Kaede Hiruma Masayuki Tasaki Yoshihiko Tomita |
| author_sort | Masaki Murata |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:55:26Z |
| format | Article |
| id | doaj.art-9ac6ea5ad56e4068bf42bd8b1f8af74a |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T22:55:26Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-9ac6ea5ad56e4068bf42bd8b1f8af74a2023-11-19T10:05:01ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-09-014597432744810.3390/cimb45090470MicroRNAs as Potential Regulators of GSK-3β in Renal Cell CarcinomaMasaki Murata0Vladimir Bilim1Yuko Shirono2Akira Kazama3Kaede Hiruma4Masayuki Tasaki5Yoshihiko Tomita6Department of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanThe 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.https://www.mdpi.com/1467-3045/45/9/470renal cell carcinomacompeting endogenous RNAmicroRNAhsa-miR-4465GSK-3β |
| spellingShingle | Masaki Murata Vladimir Bilim Yuko Shirono Akira Kazama Kaede Hiruma Masayuki Tasaki Yoshihiko Tomita MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma Current Issues in Molecular Biology renal cell carcinoma competing endogenous RNA microRNA hsa-miR-4465 GSK-3β |
| title | MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma |
| title_full | MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma |
| title_fullStr | MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma |
| title_full_unstemmed | MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma |
| title_short | MicroRNAs as Potential Regulators of GSK-3β in Renal Cell Carcinoma |
| title_sort | micrornas as potential regulators of gsk 3β in renal cell carcinoma |
| topic | renal cell carcinoma competing endogenous RNA microRNA hsa-miR-4465 GSK-3β |
| url | https://www.mdpi.com/1467-3045/45/9/470 |
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