Jing Quan1, Xiang Pan2, Yawen Li3, Yimin Hu4, Lingzhi Tao5, Zuwei Li6, Liwen Zhao7, Jingyao Wang8, Hang Li9, Yulin Lai10, Liang Zhou11, Canbin Lin12, Yaoting Gui13, Jing Ye14, Fangting Zhang15, Yongqing Lai16. 1. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Anhui Medical University, Hefei, Anhui, 230032, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: quanjing1993@hotmail.com. 2. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Anhui Medical University, Hefei, Anhui, 230032, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 1849654850@qq.com. 3. Anhui Medical University, Hefei, Anhui, 230032, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: liyawen0918@163.com. 4. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 846523886@qq.com. 5. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 3588023632@qq.com. 6. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 13592854057@163.com. 7. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Anhui Medical University, Hefei, Anhui, 230032, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 897559186@qq.com. 8. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: wangjingyao2002@bjmu.edu.cn. 9. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 413089962@qq.com. 10. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 13613611@qq.com. 11. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 763050941@qq.com. 12. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 771015222@qq.com. 13. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 18565797816@163.com. 14. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 1258382592@qq.com. 15. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: 1722403360@qq.com. 16. Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address: yqlord@outlook.com.
Abstract
BACKGROUND: Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value. METHODS: In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC. The bioinformatics analysis, RT-qPCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-23a-3p and its potential targets. Moreover, we analyzed the relationship between miR-23a-3p expression and clinicopathological variables or overall survival (OS) from 118 formalin-fixed paraffin-embedded RCC samples. RESULTS: miR-23a-3p is significantly up-regulated in RCC tissue samples, RCC cell lines and the TCGA database. Upregulating miR-23a-3p enhances, while silencing miR-23a-3p suppresses cell viability, proliferation and mobility in ACHN and 786-O cell lines. Besides, overexpression of miR-23a-3p inhibits the cell apoptosis. Then our study further reveals that miR-23a-3p regulates tumorigenesis by targeting Proline-Rich Nuclear Receptor Coactivator 2 (PNRC2). Also, the cox proportional hazard regression analysis indicates that low expression of miR-23a-3p patients has a remarkable longer OS. CONCLUSIONS: Our results reveals that miR-23a-3p may not only serve as a new biomarker for prognosis but also serve as a new therapeutic strategy in the RCC treatment.
BACKGROUND:Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value. METHODS: In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC. The bioinformatics analysis, RT-qPCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-23a-3p and its potential targets. Moreover, we analyzed the relationship between miR-23a-3p expression and clinicopathological variables or overall survival (OS) from 118 formalin-fixed paraffin-embedded RCC samples. RESULTS: miR-23a-3p is significantly up-regulated in RCC tissue samples, RCC cell lines and the TCGA database. Upregulating miR-23a-3p enhances, while silencing miR-23a-3p suppresses cell viability, proliferation and mobility in ACHN and 786-O cell lines. Besides, overexpression of miR-23a-3p inhibits the cell apoptosis. Then our study further reveals that miR-23a-3p regulates tumorigenesis by targeting Proline-Rich Nuclear Receptor Coactivator 2 (PNRC2). Also, the cox proportional hazard regression analysis indicates that low expression of miR-23a-3p patients has a remarkable longer OS. CONCLUSIONS: Our results reveals that miR-23a-3p may not only serve as a new biomarker for prognosis but also serve as a new therapeutic strategy in the RCC treatment.
Authors: Siri H Strand; Linnéa Schmidt; Simone Weiss; Michael Borre; Helle Kristensen; Anne Karin Ildor Rasmussen; Tina Fuglsang Daugaard; Gitte Kristensen; Hein Vincent Stroomberg; Martin Andreas Røder; Klaus Brasso; Peter Mouritzen; Karina Dalsgaard Sørensen Journal: Sci Rep Date: 2020-07-01 Impact factor: 4.379