PMID- 34285193 OWN - NLM STAT- MEDLINE DCOM- 20220126 LR - 20221227 IS - 2041-4889 (Electronic) VI - 12 IP - 8 DP - 2021 Jul 20 TI - High-throughput sequencing identified circular RNA circUBE2K mediating RhoA associated bladder cancer phenotype via regulation of miR-516b-5p/ARHGAP5 axis. PG - 719 LID - 10.1038/s41419-021-03977-1 [doi] LID - 719 AB - Bladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p. CI - (c) 2021. The Author(s). FAU - Yang, Chen AU - Yang C AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. YangC_Huashan@163.com. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. YangC_Huashan@163.com. AD - National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China. YangC_Huashan@163.com. FAU - Mou, Zezhong AU - Mou Z AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Wu, Siqi AU - Wu S AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Ou, Yuxi AU - Ou Y AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Zheyu AU - Zhang Z AUID- ORCID: 0000-0003-1907-0765 AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Chen, Xinan AU - Chen X AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Dai, Xiyu AU - Dai X AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Xu, Chenyang AU - Xu C AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. FAU - Mao, Shanhua AU - Mao S AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. maoshanhua@163.com. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. maoshanhua@163.com. FAU - Jiang, Haowen AU - Jiang H AUID- ORCID: 0000-0002-5349-1363 AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. haowj_sh@fudan.edu.cn. AD - Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. haowj_sh@fudan.edu.cn. AD - National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China. haowj_sh@fudan.edu.cn. LA - eng GR - 82071703/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 81802569/National Natural Science Foundation of China (National Science Foundation of China)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210720 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (ARHGAP5 protein, human) RN - 0 (GTPase-Activating Proteins) RN - 0 (MIRN516 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (Transforming Growth Factor beta) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM EIN - Cell Death Dis. 2022 Dec 22;13(12):1066. PMID: 36550098 MH - Base Sequence MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Down-Regulation/genetics MH - Epithelial-Mesenchymal Transition MH - GTPase-Activating Proteins/*metabolism MH - *Gene Expression Regulation, Neoplastic MH - Gene Silencing MH - *High-Throughput Nucleotide Sequencing MH - Humans MH - MicroRNAs/genetics/*metabolism MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Phenotype MH - Phosphorylation MH - Prognosis MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Circular/genetics/*metabolism MH - Signal Transduction MH - Transforming Growth Factor beta/metabolism MH - Tumor Burden MH - Up-Regulation/genetics MH - Urinary Bladder Neoplasms/*genetics/*pathology MH - rhoA GTP-Binding Protein/*metabolism PMC - PMC8292476 COIS- The authors declare no competing interests. EDAT- 2021/07/22 06:00 MHDA- 2022/01/27 06:00 PMCR- 2021/07/20 CRDT- 2021/07/21 05:50 PHST- 2021/02/16 00:00 [received] PHST- 2021/05/28 00:00 [accepted] PHST- 2021/07/21 05:50 [entrez] PHST- 2021/07/22 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/07/20 00:00 [pmc-release] AID - 10.1038/s41419-021-03977-1 [pii] AID - 3977 [pii] AID - 10.1038/s41419-021-03977-1 [doi] PST - epublish SO - Cell Death Dis. 2021 Jul 20;12(8):719. doi: 10.1038/s41419-021-03977-1.