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.

中文翻译：

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circTLK1通过调节miR-495-3p / CBL轴促进肾细胞癌的增殖和转移

肾细胞癌（RCC）是一种常见的泌尿外科恶性肿瘤。环状RNA（circRNA）已被证实在各种癌症中起着重要的调节作用。本研究旨在探讨circTLK1（hsa_circ_0004442）在RCC中的作用和潜在机制。通过定量逆转录聚合酶链反应或蛋白质印迹检测circTLK1，Cbl原癌基因（CBL）和microRNA-495-3p（miR-495-3p）的水平。通过集落形成，流式细胞术，划痕和transwell测定法评估细胞增殖，周期停滞和凋亡，迁移和侵袭。E-钙粘蛋白和波形蛋白的水平通过蛋白质印迹法测量。通过双荧光素酶报告基因分析证实了miR-495-3p和miR-495-3p或CBL之间的靶向关系。通过异种移植测定法评估体内肿瘤的生长。结果发现，circTLK1和CBL在RCC组织和细胞中被上调。沉默circTLK1或CBL可抑制RCC细胞的增殖和转移并加速细胞凋亡。另外，circTLK1直接与miR-495-3p结合，而CBL是miR-495-3p的靶标。circTLK1用海绵擦拭miR-495-3p以增加CBL表达。此外，敲除circTLK1可以抑制体内肿瘤的生长。总之，通过调节miR-495-3p / CBL轴，circTLK1的下调抑制了RCC细胞的增殖和转移，并促进了细胞凋亡。circTLK1用海绵擦拭miR-495-3p以增加CBL表达。此外，敲除circTLK1可以抑制体内肿瘤的生长。总之，通过调节miR-495-3p / CBL轴，circTLK1的下调抑制了RCC细胞的增殖和转移，并促进了细胞凋亡。circTLK1用海绵擦拭miR-495-3p以增加CBL表达。此外，敲除circTLK1可以抑制体内肿瘤的生长。总之，通过调节miR-495-3p / CBL轴，circTLK1的下调抑制了RCC细胞的增殖和转移，并促进了细胞凋亡。