miR-1-3p Contributes to Cell Proliferation and Invasion by Targeting Glutaminase in Bladder Cancer Cells
Background/Aims: Increasing evidence showed that miR-1-3p plays a major role in malignant tumor progression. However, the specific biological function of miR-1-3p in bladder cancer is yet unknown. Methods: The expression levels of miR-1-3p in bladder cancer tissues and cell lines were examined by qR...
Main Authors: | , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Cell Physiol Biochem Press GmbH & Co KG
2018-11-01
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Series: | Cellular Physiology and Biochemistry |
Subjects: | |
Online Access: | https://www.karger.com/Article/FullText/495273 |
Summary: | Background/Aims: Increasing evidence showed that miR-1-3p plays a major role in malignant tumor progression. However, the specific biological function of miR-1-3p in bladder cancer is yet unknown. Methods: The expression levels of miR-1-3p in bladder cancer tissues and cell lines were examined by qRT-PCR. Bisulfite sequencing PCR was used for DNA methylation analysis. The target of miR-1-3p was validated by a dual luciferase reporter assay, and the effects of miR-1-3p on phenotypic changes in bladder cancer cells were investigated in vitro and in vivo. Results: The expression of miR-1-3p in bladder cancer cells was downregulated as compared to normal SV-HUC-1 cells. Also, the expression of miR-1-3p was significantly lower in bladder cancer tissues than the corresponding non-cancerous tissues. The methylation status of CpG islands was involved in the regulation of miR-1-3p expression. miR-1-3p inhibited the bladder cancer cell proliferation, migration, and invasion by directly targeting the 3’-UTR of glutaminase. It also exerted an anti-tumor effect by negatively regulating the glutaminase in a xenograft mouse model. Furthermore, GLS depletion resulted in the prolonged expression of γH2AX. Conclusion: Taken together, these results demonstrated that miR-1-3p acts as a tumor suppressor via regulation of glutaminase expression in bladder cancer progression, and miR-1-3p might represent a novel therapeutic target for the treatment of bladder cancer. |
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ISSN: | 1015-8987 1421-9778 |