Circular RNA circ- ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic fac
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RESEARCH
Open Access
Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/ p21 axis and acts as a prognostic factor of recurrence Junming Bi1,2†, Hongwei Liu3†, Wei Dong4†, Weibin Xie1,2†, Qingqing He1,2, Zijian Cai1,2, Jian Huang1,2* and Tianxin Lin1,2*
Abstract Background: Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods: Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results: Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions: These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/ miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression. Keywords: Circ-ZKSCAN1, Bladder cancer, miR-1178-3p, p21
* Correspondence: [email protected]; [email protected] † Junming Bi, Hongwei Liu, Wei Dong and Weibin Xie contributed equally to this work. 1 Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107.W. Yanjiang Road, Guangzhou, Guangdong 510120, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) ap
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