PMID- 36331809 OWN - NLM STAT- MEDLINE DCOM- 20230425 LR - 20230517 IS - 1460-2180 (Electronic) IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 43 IP - 12 DP - 2022 Dec 31 TI - LncRNA GAS5 regulates the Wnt/beta-catenin pathway through the miR-18a-5p/AXIN2/GSK3beta axis to inhibit the proliferation and migration of bladder cancer cells. PG - 1176-1189 LID - 10.1093/carcin/bgac087 [doi] AB - LncRNA growth arrest specific 5 (GAS5) has been confirmed to play an essential role in a number of biological processes, such as tumor regulation and gene transcription. GAS5 has been shown to be a tumor suppressor gene in many types of cancer, but its specific mechanism of action in bladder cancer (BC) remains to be elucidated. In this study, we explored the biological properties of GAS5 in BC and its mechanism of action in BC. We analyzed the expression of GAS5 in 50 pairs of BC tissues and found that GAS5 was low expressed in BC tissues compared with normal mucosal tissues. In vitro and in vivo experiments showed that GAS5 could affect the proliferation and migration of BC cells. Nucleoplasmic isolation assays and fluorescence in situ hybridization (FISH) assays demonstrated the localization of GAS5 in cell cytoplasm. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP) and luciferase assay demonstrated the target binding relationship of GAS5 with miR-18a-5p. Rescue experiments demonstrated that GAS5 promoted the proliferation and migration of BC cells through target binding of miR-18a-5p. Moreover, miR-18a-5p bound to its targets AXIN2 and GSK3beta, which in turn affected the expression of Wnt/beta-catenin pathway-related proteins. Our findings demonstrate that GAS5 regulates Wnt/beta-catenin pathway activity by regulating the miR-18a-5p/AXIN2/GSK3beta axis to modulate BC progression, providing a new potential therapeutic strategy for the treatment of BC. CI - (c) The Author(s) 2022. Published by Oxford University Press. FAU - Zhang, Ze AU - Zhang Z AUID- ORCID: 0000-0001-6335-6491 AD - Department of Urology, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, P. R. China. AD - Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China. AD - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui Province, 241000, China. FAU - Liu, Tiantian AU - Liu T AUID- ORCID: 0000-0002-8654-9912 AD - Department of Urology, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, P. R. China. AD - Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China. AD - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui Province, 241000, China. FAU - Cheng, Chao AU - Cheng C AD - Department of Urology, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, P. R. China. AD - Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China. AD - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui Province, 241000, China. FAU - Wang, Jiawei AU - Wang J AD - Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China. AD - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui Province, 241000, China. FAU - Wang, Chong AU - Wang C AD - Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China. AD - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui Province, 241000, China. FAU - Huang, Houbao AU - Huang H AD - Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China. FAU - Li, Yawei AU - Li Y AD - Department of Urology, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, P. R. China. AD - Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (beta Catenin) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - 0 (AXIN2 protein, human) RN - 0 (Axin Protein) RN - 0 (MIRN18A microRNA, human) SB - IM MH - Humans MH - *MicroRNAs/genetics/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - beta Catenin/genetics/metabolism MH - Glycogen Synthase Kinase 3 beta/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - *Urinary Bladder Neoplasms/genetics MH - Cell Proliferation/genetics MH - Cell Line, Tumor MH - Gene Expression Regulation, Neoplastic MH - Cell Movement/genetics MH - Axin Protein/genetics/metabolism PMC - PMC10122427 COIS- The authors declare that they have no conflict of interest. EDAT- 2022/11/05 06:00 MHDA- 2023/04/25 10:20 PMCR- 2022/11/04 CRDT- 2022/11/04 12:23 PHST- 2022/06/30 00:00 [received] PHST- 2022/10/18 00:00 [revised] PHST- 2022/11/04 00:00 [accepted] PHST- 2023/04/25 10:20 [medline] PHST- 2022/11/05 06:00 [pubmed] PHST- 2022/11/04 12:23 [entrez] PHST- 2022/11/04 00:00 [pmc-release] AID - 6798911 [pii] AID - bgac087 [pii] AID - 10.1093/carcin/bgac087 [doi] PST - ppublish SO - Carcinogenesis. 2022 Dec 31;43(12):1176-1189. doi: 10.1093/carcin/bgac087.