Increasing evidence has indicated that circular RNAs (circRNAs) play a key role in the development and progression of diverse cancers, but their role in clear cell renal carcinoma (CCRCC) tumorigenesis is not well understood. In this study, we firstly performed comprehensive circRNA-seq from CCRCC tissues and pair-matched adjacent normal tissues. In total, 1184 circRNAs were dysregulated in human CCRCC tissues compared with those in adjacent normal tissues. We randomly selected four circRNAs, including circHIPK3 (circBase ID: hsa_circ_0000284), to test the circRNA-seq data in another 40 CCRCC tissues by quantitative real-time PCR (qRT-PCR). Furthermore, we found that circHIPK3 was downregulated in CCRCC tissues and cell lines. Overexpression of circHIPK3 effectively suppressed CCRCC cell invasion and migration in vitro, and inhibited CCRCC cell proliferation in vitro and in vivo. Moreover, bioinformatic analysis and luciferase reporter assay showed that circHIPK3 targeted miR-637 in CCRCC cells. Hence, CircHIPK3 may represent a tumor suppressor and target miR-637 in clear cell renal carcinoma.

中文翻译：

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透明细胞肾癌中circRNA的全面分析和circHIPK3的抑癌功能。

越来越多的证据表明，环状RNA（circRNA）在多种癌症的发生和发展中起着关键作用，但是它们在透明细胞肾癌（CCRCC）肿瘤发生中的作用尚不清楚。在这项研究中，我们首先从CCRCC组织和成对匹配的邻近正常组织中进行了全面的circRNA-seq。与邻近的正常组织相比，在人类CCRCC组织中总共有1184个circRNA失调。我们随机选择了四个circRNA，包括circHIPK3（circBase ID：hsa_circ_0000284），以通过定量实时PCR（qRT-PCR）在另外40个CCRCC组织中测试circRNA-seq数据。此外，我们发现circHIPK3在CCRCC组织和细胞系中被下调。circHIPK3的过表达可有效抑制CCRCC细胞在体外的侵袭和迁移，并在体外和体内抑制CCRCC细胞增殖。此外，生物信息学分析和荧光素酶报告基因分析表明，circHIPK3靶向CCRCC细胞中的miR-637。因此，CircHIPK3可能代表透明细胞肾癌中的肿瘤抑制因子和靶标miR-637。