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.
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Acknowledgements
The study was supported by grants from the National Key Research and Development Program of China (No. 2016YFC1305703), the Medical Scientific Research Foundation of Guangdong Province, China (No. A2019571), the Fundamental Research Funds for the Central Universities(No. 21618303), the Science and technology project of Yangjiang city (No. 33518008 to Dr Lai), Leading Specialist Construction Project-Department of Urology, the First Affiliated Hospital, Jinan University (No. 711006) and the Fundamental Research Funds for the Central Universities (No. 21618306). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
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LHM performed the experiments, collected and analyzed the data, and drafted the manuscript. OYP and XXX performed the experiment and analyzed the data, CG, CZ, ZKH and ZTS performed the experiment. LCY and HBL designed the study, analyzed the data and revised the manuscript. All authors read and approved the final manuscript.
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All of the samples (clear cell renal carcinoma tissues and pair-matched adjacent normal tissues) were obtained with appropriate informed consent from the patients and were approved by the Ethical Committee of The First Affiliated Hospital of Jinan University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethical Committee of The First Affiliated Hospital of Jinan University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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The animal studies were approved by the committee on animal experimentation of Jinan University. All procedures performed in studies involving animals were in accordance with the ethical standards of the committee on animal experimentation of Jinan University.
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Li, H., Heng, B., Ouyang, P. et al. Comprehensive profiling of circRNAs and the tumor suppressor function of circHIPK3 in clear cell renal carcinoma. J Mol Hist 51, 317–327 (2020). https://doi.org/10.1007/s10735-020-09882-9
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DOI: https://doi.org/10.1007/s10735-020-09882-9