Exosomal circular RNA_400068 promotes the development of renal cell carcinoma via the miR-210-5p/SOCS1 axis

Abstract

Renal cell carcinoma (RCC) is a common type of malignancy in the kidney, which accounts for ~80% of the cases within adult patients. The pathogenesis of RCC is complicated and involves alterations at both genetic and epigenetic levels. The aim of the present study was to investigate the roles of circRNAs in the pathogenesis of RCC. In the current study, exosomes were isolated via gradient centrifugation and identified using transmission electron microscope. The expression levels of circular RNA (circ)_400068, microRNA (miR)-210-5p and suppressor of cytokine signaling 1 (SOCS1) were examined using reverse transcription-quantitative PCR. Cell proliferation was evaluated using a Cell Counting Kit-8 assay, and the apoptotic rate was determined in transfected cells using flow cytometry. The protein expression levels of proliferation- and apoptosis-associated genes were assessed via western blot analysis. Upregulation of circ_400068 was detected in RCC plasma exosomes, tissue samples and cells. Additionally, treatment with exosomal circ_400068 promoted the proliferation and inhibited the apoptosis of healthy kidney cells, which were abrogated by short hairpin RNA-circ_400068. The results suggested that miR-210-5p was a potential downstream molecule of circ_400068, and SOCS1 was a novel target of miR-210-5p. Moreover, circ_400068 regulated the proliferation of HK-2 cells by targeting the miR-210-5p/SOCS1 axis, as the effects on cell proliferation caused by treatment using exosomes isolated from the culture media of RCC cells were abolished by miR-210-5p mimics. It was found that enhanced cell proliferation induced by miR-210-5p inhibitors was attenuated by the knockdown of SOCS1, while the influences triggered by miR-210-5p mimics were reversed by SOCS1 overexpression. Collectively, the present findings provided a novel insight into the crucial regulatory functions of circ_400068 in RCC, and the circ_400068/miR-210-5p/SOCS1 axis could be a candidate therapeutic target for the treatment of patients with RCC.