Authors

Mei Yan Yu*, Lian Shun Cui*, Chang Hai Sun**,#

Departments

*Department of Nephrology, Weihai central hospital, 264400, Weihai, China - **Department of Urology, Weihai central hospital, 264400, Weihai, China

Abstract

Background: Renal cell carcinoma (RCC) is one of the common urological tumors with a poor prognosis. Long noncoding RNA Cancer Susceptibility Candidate 2 (CASC2) is concerned with the progression of multiple cancers, but the underlying molecular mechanism of CASC2 in RCC is still largely unclear. 

Methods: The expression levels of CASC2, miRNA-27a-3p, and schlafen 5 (SLFN5) mRNA were detected using quantitative real time polymerase chain reaction (qRT-PCR). The expression levels of SLFN5 protein in RCC cells were measured with Western blot. The proliferation, apoptosis, migration, and invasion of RCC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell, or flow cytometry assays. The relationship between miR-27a-3p and CASC2 or SLFN5 were predicted by the miRcode or TargetScan 7.2 database and confirmed with dual luciferase reporter system.

Results: We observed that CASC2 and SLFN5 were down-regulated while miR-27a-3p was up-regulated in RCC tissues and cells compared to the adjacent normal tissues and the HEK-293 cells (P < 0.05). Besides, we discovered that CASC2 overexpression restrained cell proliferation, migration, invasion, and facilitated cell apoptosis in RCC cells through gain-of-function experiments (P < 0.05). Notably, CASC2 was verified as a sponge for miR-27a-3p and SLFN5 acted as a downstream target for miR-27a-3p. We found that CASC2 regulated SLFN5 expression via sponging miR-27a-3p in RCC cells through western blot. In addition, miR-27a-3p overexpression undermined CASC2 elevation-mediated effects on the proliferation, apoptosis, migration, and invasion of RCC cells (P < 0.05). Also, the effects of miR-27a-3p overexpression on the malignant behaviors of RCC cells were abolished by SLFN5 enhancement (P < 0.05).

Conclusion: CASC2 overexpression  could block the advancement of RCC through upregulating SLFN5 via sponging miR-27a-3p, and CASC2 might be a potential target for the improvement of the prognosis of RCC patients of RCC.

Keywords

RCC, CASC2, miR-27a-3p, SLFN5.

DOI:

10.19193/0393-6384_2020_3_320