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Circular RNA RBPMS inhibits bladder cancer progression via miR-330-3p/RAI2 regulation.

ABSTRACT: Bladder cancer is a severe cancer with high mortality because of invasion and metastasis. Growing evidence has revealed that circular RNAs play critical roles in biological function, which is closely connected to proliferation and invasion of bladder cancer. In our study, we employed qRT-PCR, RNA fluorescence in situ hybridization (FISH), 5-ethynyl-2'-deoxyuridine (EdU), CCK-8, Transwell assays, luciferase reporter assays, xenografts, and live imaging to detect the roles of circular RNA binding protein with multiple splicing (circRBPMS) in bladder cancer (BC). Bioinformatics analysis and WB were performed to investigate the regulatory mechanism. Expression profile analysis of circular RNAs (circRNAs) in BC revealed that circRBPMS was significantly downregulated. Low circRBPMS expression correlates with aggressive BC phenotypes, whereas upregulation of circRBPMS suppresses BC cell proliferation and metastasis by directly targeting the miR-330-3p/ retinoic acid induced 2 (RAI2) axis. miR-330-3p upregulation or silencing of RAI2 restored BC cell proliferation, invasion, and migration following overexpression of circRBPMS. RAI2 silencing reversed miR-330-3p-induced cell invasion and migration as well as growth inhibition in vitro. Moreover, through bioinformatic analysis of the downstream target of RAI2 in the TCGA database, we identified and validated the biological role of circRBPMS through the RAI2-mediated ERK and epithelial-mesenchymal transition (EMT) pathways. We summarize the circRBPMS/miR-330-3p/RAI2 axis, where circRBPMS acts as a tumor suppressor, and provide a potential biomarker and therapeutic target for BC.

SUBMITTER: Yang C

PROVIDER: S-EPMC7868720 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Circular RNA RBPMS inhibits bladder cancer progression via miR-330-3p/RAI2 regulation.

Yang Chen C Mou Zezhong Z Zhang Zheyu Z Wu Siqi S Zhou Quan Q Chen Yiling Y Gong Jian J Xu Chenyang C Ou Yuxi Y Chen Xinan X Dai Xiyu X Jiang Haowen H

Molecular therapy. Nucleic acids 20210116

Bladder cancer is a severe cancer with high mortality because of invasion and metastasis. Growing evidence has revealed that circular RNAs play critical roles in biological function, which is closely connected to proliferation and invasion of bladder cancer. In our study, we employed qRT-PCR, RNA fluorescence <i>in situ</i> hybridization (FISH), 5-ethynyl-2'-deoxyuridine (EdU), CCK-8, Transwell assays, luciferase reporter assays, xenografts, and live imaging to detect the roles of circular RNA b ...[more]

PMID: 33614236

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Project description:BackgroundBreast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.MethodsThe levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.ResultsHsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.ConclusionHsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.

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Circular RNA RBPMS inhibits bladder cancer progression via miR-330-3p/RAI2 regulation.

Publications

Circular RNA RBPMS inhibits bladder cancer progression via miR-330-3p/RAI2 regulation.

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