CircTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis.

Xiangli Lei,Shuai Tan,Meiling Yang,Heng Zhang,Zhifang Xiao

doi:10.1515/biol-2021-0041

Abstract

Renal cell carcinoma (RCC) is a common urological malignancy. Circular RNAs (circRNAs) have been confirmed to play an important regulatory role in various cancers. This study aimed to investigate the role and potential mechanism of circTLK1 (hsa_circ_0004442) in RCC. The levels of circTLK1, Cbl proto-oncogene (CBL), and microRNA-495-3p (miR-495-3p) were detected by quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation, cycle arrest and apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, scratch, and transwell assays. The levels of E-cadherin and Vimentin were measured by western blot. The targeting relationship between miR-495-3p and miR-495-3p or CBL was verified by dual-luciferase reporter assay. Tumor growth in vivo was evaluated by xenograft assay. The results found that circTLK1 and CBL were up-regulated in RCC tissues and cells. Silencing of circTLK1 or CBL inhibited proliferation and metastasis and accelerated apoptosis in RCC cells. In addition, circTLK1 directly bound to miR-495-3p, and CBL was the target of miR-495-3p. circTLK1 sponged miR-495-3p to increase CBL expression. Moreover, knockdown of circTLK1 suppressed tumor growth in vivo. In conclusion, down-regulation of circTLK1 restrained proliferation and metastasis and promoted apoptosis in RCC cells by modulating miR-495-3p/CBL axis.

Highlights

Renal cell carcinoma (RCC) is a urologic malignancy originating from the renal epithelium, which accounts for more than 90% of renal cancers [1]
In view of the functions of circTLK1 and Cbl proto-oncogene (CBL) in RCC cells, we further explored whether the influence of circTLK1 on RCC cell progression is related to CBL
Si-circTLK1 and cells to investigate their effects on RCC cell progression. pcDNA-CBL were co-transfected into Caki-1 and 786-O The results showed that knockdown of circTLK1 markedly impeded cell proliferation (Figure 4b) and induced cell cycle arrest (Figure 4c) and apoptosis (Figure 4d) in Caki-1 and 786-O cells, while these effects were abolished by up-regulating CBL

Summary

Introduction

Renal cell carcinoma (RCC) is a urologic malignancy originating from the renal epithelium, which accounts for more than 90% of renal cancers [1]. It is estimated that there were 403,262 new kidney cancer cases and 175,098 related deaths worldwide in 2018 [2]. RCC is a genitourinary malignant tumor with a mortality rate second only to bladder cancer [3]. Targeted therapies have become the main treatment for patients with recurrent or metastatic RCC [4]. Because of the radioresistance and chemoresistance of RCC, the 5-year survival rate of metastatic RCC is still as low as about 10% [5]. Exploring the potential mechanism of RCC pathogenesis is essential for the development of effective RCC treatment strategies

Objectives

Results

Conclusion