miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1

Yongpeng Xie; Luyao Chen; Yu Gao; Xin Ma; Weiyang He; Yu Zhang; Fan Zhang; Yang Fan; Liangyou Gu; Pin Li; Xu Zhang; Xin Gou

doi:10.1186/s12935-020-01313-9

miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1

Cancer Cell Int. 2020 Jun 10:20:227. doi: 10.1186/s12935-020-01313-9. eCollection 2020.

Authors

Yongpeng Xie^#¹, Luyao Chen^#², Yu Gao³, Xin Ma³, Weiyang He¹, Yu Zhang³, Fan Zhang³, Yang Fan³, Liangyou Gu³, Pin Li⁴, Xu Zhang³, Xin Gou¹

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016 China.
² Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi China.
³ Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100853 China.
⁴ Department of Pediatric Urology, Bayi Children's Hospital Affiliated to the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.

^# Contributed equally.

Abstract

Background: MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC).

Methods: The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses.

Results: we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression.

Conclusions: Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC.

Keywords: Clear cell renal cell carcinoma; Invasion; Migration; Proliferation; S1PR1; miR-363.