MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Wang,Wei; Hu,Wentao; Wang,Ya; Yang,Jing; Yue,Zhongjin

doi:10.3892/etm.2019.7332

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Authors:
- Wei Wang
- Wentao Hu
- Ya Wang
- Jing Yang
- Zhongjin Yue
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Affiliations: Department of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu 730000, P.R. China, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of Nephrology, Lanzhou University Second Hospital, Lanzhou, Gansu 730000, P.R. China, Clinical Laboratory, Lanzhou University Second Hospital, Lanzhou, Gansu 730000, P.R. China
Published online on: March 1, 2019 https://doi.org/10.3892/etm.2019.7332
Pages: 3814-3822

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Abstract

Recent studies have identified several microRNAs (miRNAs/miRs) that are dysregulated in clear cell renal cell carcinoma (ccRCC), and their dysregulation may serve important roles in the occurrence and development of ccRCC. Therefore, understanding the expression pattern and functional roles of miRNAs in ccRCC may facilitate the identification of novel therapeutic targets for the treatment of ccRCC. In the current study, reverse transcription‑quantitative polymerase chain reaction was used to determine miR‑508 expression levels in ccRCC tissue samples and cell lines. The cell counting kit‑8 and in vitro Transwell invasion assays were used to examine the effects of miR‑508 overexpression on ccRCC cell proliferation and invasion, respectively. In addition, bioinformatics analysis and dual‑luciferase reporter gene assays were used to investigate the underlying mechanism of miR‑508 in ccRCC cells. Furthermore, the regulatory role of miR‑508 on zinc finger E‑box‑binding homeobox 1 (ZEB1) mRNA and protein expression in ccRCC cells was investigated using RT‑qPCR and western blot analysis, respectively. Additionally, the association between miR‑508 and ZEB1 expression in ccRCC tissue samples was examined. Rescue experiments were performed to determine whether the tumor suppressive effects of miR‑508 may be mediated by ZEB1 in ccRCC cells. The results of the current study demonstrated that miR‑508 expression was significantly downregulated in ccRCC tissue samples and cell lines. In addition, miR‑508 overexpression significantly decreased the proliferation and invasion of ccRCC cells. ZEB1 was identified as a direct target gene of miR‑508 in ccRCC cells and the relative expression level of ZEB1 mRNA was significantly increased in ccRCC tissue samples. Furthermore, a negative correlation between miR‑508 and ZEB1 expression was identified in ccRCC tissues. ZEB1 knockdown exhibited a functional role similar to miR‑508 overexpression in ccRCC cells, and restoration of ZEB1 expression significantly reversed the inhibitory effects of miR‑508 on the malignant phenotype of ccRCC cells. Taken together, the results of the current study demonstrated that miR‑508 may serve a tumor suppressive role in ccRCC via direct targeting of ZEB1. MiR‑508 may present a novel and efficient therapeutic target for the treatment of patients with ccRCC.

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