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

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ORIGINAL PAPER

Comprehensive profiling of circRNAs and the tumor suppressor function of circHIPK3 in clear cell renal carcinoma Haomin Li1 · Baoli Heng2,5   · Peng Ouyang1 · Xuexia Xie1 · Tingshun Zhang1 · Guo Chen1 · Zheng Chen1 · Kahong Cheang3 · Caiyong Lai1,4 Received: 26 December 2019 / Accepted: 9 May 2020 © Springer Nature B.V. 2020

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. Keywords  CircRNA · Circular RNA · CircHIPK3 · miR-637 · Clear cell renal carcinoma · Renal carcinoma

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1073​5-020-09882​-9) contains supplementary material, which is available to authorized users. * Baoli Heng [email protected] * Caiyong Lai [email protected] 1



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

2



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

3

Centor Medico Kong, Wa‑Estrada do Arco NO. S124, Ki Kuan Bairro, AZ, Macau

4

Yang Xi General Hospital People’s Hospital, Yangjiang, China

5

Department of Urology, People’s Hospital of Yingde City, Yingde, China



Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, representing approximately 2–3% of all adult malignancies (Cohen and McGovern 2005). Clear cell renal cell carcinoma (CCRCC) is the most common type of RCC, which accounts for 60–85% of all RCC cases (Bray et al. 2018). Current imaging methods, such as computed tomography (CT), have been able to detect more and more small renal masses, but CCRCC is insidious and about 30% patients will develop local invasion and distant metastatic lesions even after the tumors are found (Ljungberg et al. 2011; Znaor et al. 2015). Hence, these CCRCC patients have already lost their chances of radical surgical resection upon lesion detection and exhibit a low 5-year survival rate. Therefore, novel prognostic biomarkers and