Background: Circular RNAs (circRNAs) are a new class of non-coding RNAs (ncRNAs) that are derived from exons or introns by special selective shearing. circRNAs have been shown to play critical roles in various human cancers. However, their roles in renal cell carcinoma (RCC) and the underlying mechanisms remain largely unknown./nMethods: A novel circRNA-circPTCH1, was identified from a microarray analysis of five paired RCC tissues. Then, we validated its expression and characterization through qRT-PCR, gel electrophoresis, RNase R digestion assays and Sanger sequencing. Functional experiments were performed to determine the effect of circPTCH1 on RCC progression both in vitro and in vivo. The interactions between circPTCH1 and miR-485-5p were clarified by RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays./nResults: We observed that circPTCH1 was up-regulated in RCC cell lines and tumor samples, and higher levels of circPTCH1 were significantly correlated with worse patient survival, advanced Fuhrman grade and greater risk of metastases. Elevated circPTCH1 expression led to increased migration and invasion of RCC cells both in vitro and in vivo whereas silencing circPTCH1 decreased migration and invasion and impeded the epithelial-mesenchymal transition (EMT) of RCC cells. Mechanistically, we elucidated that circPTCH1 could directly bind miR-485-5p and subsequently suppress expression of the target gene MMP14./nConclusion: circPTCH1 promotes RCC metastasis via the miR-485-5p/MMP14 axis and activation of the EMT process. Targeting circPTCH1 may represent a promising therapeutic strategy for metastatic RCC.

中文翻译：

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circPTCH1通过调节miR-485-5p/MMP14轴促进肾细胞癌的侵袭和转移。

背景：环状 RNA (circRNA) 是一类新的非编码 RNA (ncRNA)，通过特殊的选择性剪切从外显子或内含子中衍生而来。circRNA 已被证明在各种人类癌症中发挥关键作用。然而，它们在肾细胞癌 (RCC) 中的作用及其潜在机制仍然很大程度上未知。/n方法：从对五对 RCC 组织的微阵列分析中鉴定出一种新的 circRNA-circPTCH1。然后，我们通过 qRT-PCR、凝胶电泳、RNase R 消化测定和 Sanger 测序验证了其表达和表征。进行功能实验以确定 circPTCH1在体外和体内对 RCC 进展的影响. circPTCH1 和 miR-485-5p 之间的相互作用通过 RNA pull-down、荧光素酶报告基因和 RNA 免疫沉淀 (RIP) 分析得到阐明。/n结果：我们观察到 circPTCH1 在 RCC 细胞系和肿瘤样本中上调，并且更高circPTCH1 水平与更差的患者生存率、高级 Fuhrman 分级和更高的转移风险显着相关。升高的 circPTCH1 表达导致 RCC 细胞在体外和体内的迁移和侵袭增加，而沉默 circPTCH1 减少迁移和侵袭并阻碍 RCC 细胞的上皮-间质转化 (EMT)。从机制上讲，我们阐明了 circPTCH1 可以直接结合 miR-485-5p 并随后抑制靶基因 MMP14 的表达。/n结论： circPTCH1通过miR-485-5p/MMP14轴和激活EMT过程促进RCC转移。靶向 circPTCH1 可能是转移性肾细胞癌的一种有前途的治疗策略。