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环状 RNA 谱分析及 circHIPK3 在肾透明细胞癌中的抑瘤作用

Comprehensive profiling of circRNAs and the tumor suppressor function of circHIPK3 in clear cell renal carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Road, Guangzhou, China.

Yingde Center, Institute of Kidney Surgery, Jinan University, Guangdong, China.

出版信息

J Mol Histol. 2020 Jun;51(3):317-327. doi: 10.1007/s10735-020-09882-9. Epub 2020 May 14.

DOI:10.1007/s10735-020-09882-9
PMID:32409849
Abstract

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.

摘要

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,但它们在透明细胞肾细胞癌(CCRCC)肿瘤发生中的作用尚不清楚。在这项研究中,我们首先对 CCRCC 组织和配对的相邻正常组织进行了全面的 circRNA-seq 分析。与相邻正常组织相比,在人类 CCRCC 组织中共有 1184 个 circRNA 失调。我们随机选择了四个 circRNA,包括 circHIPK3(circBase ID:hsa_circ_0000284),通过定量实时 PCR(qRT-PCR)在另外 40 个 CCRCC 组织中检测 circRNA-seq 数据。此外,我们发现 circHIPK3 在 CCRCC 组织和细胞系中下调。circHIPK3 的过表达可有效抑制 CCRCC 细胞的体外侵袭和迁移,并抑制 CCRCC 细胞的体外和体内增殖。此外,生物信息学分析和荧光素酶报告基因实验表明,circHIPK3 在 CCRCC 细胞中靶向 miR-637。因此,CircHIPK3 可能在透明细胞肾细胞癌中作为肿瘤抑制因子并靶向 miR-637。

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