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Hsa_circ_101555 functions as a competing endogenous RNA of miR-597-5p to promote colorectal cancer progression

Oncogene volume 38, pages 6017–6034 (2019)Cite this article

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Abstract

CircRNAs have been reported to exert momentous roles in regulating pathophysiological process and guiding clinical diagnosis and treatment in colorectal cancer (CRC). However, there are still a lot of circRNAs that need to be unearthed. In this study, we evaluated the expression profile of circRNAs in 10 CRC tissues and their corresponding normal-appearing tissues (NATs) by microarray, and identified that hsa_circ_101555 (circ101555) was significantly up-regulated in tumor tissues and closely related to the prognosis of CRC patients. A specific close loop structure of circ101555 was described, which was generated by back-splicing of the host gene CSNK1G1 and showed greater stability than the linear RNA. The results in vitro and in vivo showed that silencing circ101555 expression significantly suppressed cell proliferation, induced apoptosis and impaired the DNA repair capacity of CRC cells, while rescue experiments suggested that down-expression of miR-597-5p could significantly attenuate the biological effects of circ101555 knockdown on CRC cells. Subsequent experiments in vitro, including double fluorescence in situ hybridization (D-FISH) analysis, RIP analysis and biotin-coupled probe pull down assay, confirmed that miR-597-5p was effectively enriched by circ101555, and circ101555 might serve as a sponge of miR-597-5p. Moreover, two putative oncogenes (CDK6 and RPA3) were identified as the miR-597-5p potential targets. Taken together, our results proved that circ101555 might function as a competing endogenous RNA of miR-597-5p to up-regulate CDK6 and RPA3 expression in CRC. Circ101555 could be a useful prognostic indicator in patients with CRC, and silence of circ101555 provided a new attractive therapeutic measure for CRC.

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Acknowledgements

This study was supported by grants from the Special Subject of Diagnosis Treatment of Key Clinical Diseases of Suzhou City Sci-tech Bureau (LCZX201401), the Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Medical Youth Talent (QNRC2016723) and Suzhou Gusu Medical Youth Talent (GSWS2019032).

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  1. These authors contributed equally: Zhenlong Chen, Rui Ren, Daiwei Wan

Authors and Affiliations

  1. Department of General Surgery, the First Affiliated Hospital of Soochow University, 215006, Suzhou, China

    Zhenlong Chen, Daiwei Wan, Xiaofeng Xue, Ye Han, Yuting Kuang & Qiaoming Zhi

  2. Department of General Surgery, the Second Affiliated Hospital of Soochow University, 215000, Suzhou, China

    Rui Ren

  3. Department of Hepatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China

    Yilin Wang

  4. Department of Oncology, the First Affiliated Hospital of Soochow University, 215006, Suzhou, China

    Min Jiang & Wei Li

  5. Department of Gastroenterology, the First Affiliated Hospital of Soochow University, 215006, Suzhou, China

    Jiaqing Shen & Fei Liu

  6. Department of Oncology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, 215002, Suzhou, China

    Jianming Shi

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Correspondence to Yilin Wang, Wei Li or Qiaoming Zhi.

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Chen, Z., Ren, R., Wan, D. et al. Hsa_circ_101555 functions as a competing endogenous RNA of miR-597-5p to promote colorectal cancer progression. Oncogene 38, 6017–6034 (2019). https://doi.org/10.1038/s41388-019-0857-8

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