OncoTargets and Therapy (Nov 2020)
LncRNA RNF144A-AS1 Promotes Bladder Cancer Progression via RNF144A-AS1/miR-455-5p/SOX11 Axis
Abstract
Huifeng Bi,1,2 Zhenhua Shang,1 Chunsong Jia,1 Jiangtao Wu,1 Bo Cui,1 Qi Wang,1 Tongwen Ou1 1Department of Urology, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China; 2Department of Urology, Jincheng General Hospital, Jincheng, Shanxi Province, People’s Republic of ChinaCorrespondence: Tongwen OuDepartment of Urology, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, People’s Republic of ChinaTel +86 135 0106 5134Fax +86 010 8319 8388Email [email protected]: Bladder cancer (BC) is the most commonly occurring malignant tumor of the urinary system worldwide. Long non-coding RNAs (lncRNAs), including lncRNA RNF144A-AS1 (RNF144A-AS1), perform an oncogenic role in BC progression. However, how RNF144A-AS1 is regulated in BC has not been fully investigated, and its role in BC is mostly obscure. In this study, we explore its role in BC progression.Materials and Methods: The expression level of RNF144A-AS1 in BC tissues was explored via bioinformatics analysis and quantitative real-time PCR (qRT-PCR). We used RNF144A-AS1 siRNA (si-RNF144A-AS1) to inhibit the RNF144A-AS1 level in BC cell lines (J82 and 5637 cells). A series of experimental studies in vitro (CCK-8 assay, colony formation assay and Transwell assay) was performed to explore the role of si-RNF144A-AS1 on the proliferation, migration and invasion of J82 and 5637 cells. A BC xenograft model was established, and the effect of si-RNF144A-AS1 on xenograft growth was explored in vivo. The interactions among RNF144A-AS1, miR-455-5p and SOX11 were predicted by bioinformatics miRanda and Targetscan database, and verified by the luciferase reporter assay and RNA pull-down assay. Finally, miR-455-5p inhibitor and si-RNF144A-AS1 were cotransfected into J82 and 5637 cells.Results: RNF144A-AS1 is overexpressed in BC tumors and cells, and its overexpression is correlated with poor prognosis. Knockdown of RNF144A-AS1 markedly suppressed the proliferation, migration and invasion of J82 and 5637 cells and significantly inhibited xenograft growth in nude mice, compared to si-NC. We found that RNF144A-AS1 serves as a sponge for miR-455-5p. Furthermore, a binding site of miR-455-5p was found in 3ʹ UTR of SOX11 gene, and overexpression of miR-455-5p suppressed SOX11 levels. RNF144A-AS1 knockdown markedly decreased SOX11 expression levels, while miR-455-5p inhibitor restored this repressive effect. Restoration of SOX11 could reverse this repressive effect of RNF144A-AS1 on cell proliferation, migration and invasion abilities.Conclusion: Overall, our findings underline the critical role of RNF144A-AS1 in BC development, and our study reveals for the first time that RNF144A-AS1 promotes BC progression via the RNF144A-AS1/miR-455-5p/SOX11 axis.Keywords: bladder cancer, lncRNA RNF144A-AS1, miRNA-455-5p, SOX11 gene, bladder cancer progression
