Junfeng Zhang1, Longsheng Wang1, Shiyu Mao1, Mengnan Liu1, Wentao Zhang1, Ziwei Zhang1, Yadong Guo1, Bisheng Huang1, Yang Yan1, Yong Huang2, Xudong Yao3. 1. Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. 2. Department of Urology, Affiliated Hospital of Inner Mongolia Medical University, Huhhot, China. 3. Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, Chinayaoxudong67@126.com.
Abstract
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.
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.
Authors: Berta Roman-Canal; Cristian Pablo Moiola; Sònia Gatius; Sarah Bonnin; Maria Ruiz-Miró; Esperanza González; Amaia Ojanguren; José Luis Recuero; Antonio Gil-Moreno; Juan M Falcón-Pérez; Julia Ponomarenko; José M Porcel; Xavier Matias-Guiu; Eva Colas Journal: Sci Rep Date: 2019-10-21 Impact factor: 4.379