PMID- 36301978 OWN - NLM STAT- MEDLINE DCOM- 20221220 LR - 20221222 IS - 1098-2299 (Electronic) IS - 0272-4391 (Linking) VI - 83 IP - 8 DP - 2022 Dec TI - Circ_0002099 is a novel molecular therapeutic target for bladder cancer. PG - 1890-1905 LID - 10.1002/ddr.22005 [doi] AB - Bladder cancer (BLCA) acts as one of the most common malignant tumors in the urinary system without ideal therapy. We performed the present study to explore the role and mechanism of Circ_0002099 in BLCA progression. RNase R treatment assay and actinomycin D treatment assay were used to confirm the circular structure of Circ_0002099. Nuclear-cytoplasmic fractionation assay and fluorescence in situ hybridization (FISH) were used to indicate the subcellular localization of Circ_0002099. The CCK-8 assay, colony formation assay, wound-healing assay, Transwell assay, and animal experiment were used to reveal the facilitative effect of Circ_0002099 on BLCA both in vitro and in vivo. Furthermore, bioinformatic analysis, western blot analysis, FISH, and dual-luciferase reporter assay were conducted to demonstrate the role of Circ_0002099 in BLCA progression. The results indicated that Circ_0002099 was significantly upregulated in BLCA and could enhance the progression of BLCA in vivo and in vitro. Furthermore, dual-luciferase reporter assay and FISH assay revealed that Circ_0002099 could regulate miR-217-5p/miR-103a-3p/Kirsten RAS (KRAS) axis in BLCA. In addition, rescue experiments confirmed that miR-217-5p/miR-103a-3p could rescue the facilitative effect of Circ_0002099 on BLCA progression. Moreover, FUS (FUSed in sarcoma) was identified to regulate the Circ_0002099-miR-217-5p/miR-103a-3p/KRAS axis in BLCA progression. The present study suggested that FUS-medicated Circ_0002099 could promote the epithelial-mesenchymal transition process in BLCA progression via miR-217-5p/miR-103a-3p/KRAS axis-WNT/beta-catenin axis. It could be a promising prognostic biomarker and therapeutic target for BLCA. CI - (c) 2022 Wiley Periodicals LLC. FAU - Fang, Ping AU - Fang P AD - Department of Oncology, The 902nd Hospital of the PLA Joint Logistics Support Force, Bengbu, China. FAU - Jiang, Qingling AU - Jiang Q AD - Department of Oncology, The PLA Navy Anqing Hospital, Anqing, China. FAU - Liu, Sizhong AU - Liu S AD - Department of Oncology, The 902nd Hospital of the PLA Joint Logistics Support Force, Bengbu, China. FAU - Gu, Jun AU - Gu J AD - Department of Oncology, The 902nd Hospital of the PLA Joint Logistics Support Force, Bengbu, China. FAU - Hu, Kai AU - Hu K AD - Department of Oncology, Radiotherapy and Chemotherapy, Guangde Traditional Chinese Medicine Hospital, Xuancheng, China. FAU - Wang, Zishu AU - Wang Z AUID- ORCID: 0000-0002-3641-3734 AD - Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. LA - eng PT - Journal Article DEP - 20221027 PL - United States TA - Drug Dev Res JT - Drug development research JID - 8204468 RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - In Situ Hybridization, Fluorescence MH - Proto-Oncogene Proteins p21(ras) MH - *Urinary Bladder Neoplasms/drug therapy/genetics MH - Epithelial-Mesenchymal Transition MH - *MicroRNAs/genetics MH - Cell Proliferation MH - Cell Line, Tumor OTO - NOTNLM OT - KRAS OT - bladder cancer OT - circRNA EDAT- 2022/10/28 06:00 MHDA- 2022/12/21 06:00 CRDT- 2022/10/27 13:56 PHST- 2022/09/27 00:00 [revised] PHST- 2022/07/27 00:00 [received] PHST- 2022/09/29 00:00 [accepted] PHST- 2022/10/28 06:00 [pubmed] PHST- 2022/12/21 06:00 [medline] PHST- 2022/10/27 13:56 [entrez] AID - 10.1002/ddr.22005 [doi] PST - ppublish SO - Drug Dev Res. 2022 Dec;83(8):1890-1905. doi: 10.1002/ddr.22005. Epub 2022 Oct 27.