PMID- 37944649 OWN - NLM STAT- MEDLINE DCOM- 20240105 LR - 20240106 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 894 DP - 2024 Feb 5 TI - LUCAT1 inhibits ferroptosis in bladder cancer by regulating the mRNA stability of STAT3. PG - 147974 LID - S0378-1119(23)00815-6 [pii] LID - 10.1016/j.gene.2023.147974 [doi] AB - OBJECT: In this study, we aimed to elucidate the role of LUCAT1, a recently identified lncRNA, in ferroptosis within the context of bladder cancer (BC). METHODS: Through a comprehensive array of experimental techniques, including transmission electron microscopy (TEM), RNA pull-down assays, and fluorescence in situ hybridization (FISH), we investigated the molecular interactions and functional consequences associated with LUCAT1 in BC cells. RESULTS: Our findings indicate that LUCAT1 acts as a pivotal regulator in BC, fostering cell proliferation, migration, and invasion, while concurrently impeding ferroptosis. Mechanistically, we unveiled a direct binding between LUCAT1 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which governs the mRNA stability of signal transducer and activator of transcription 3 (STAT3). Intriguingly, ectopic expression of STAT3 counteracted the suppressive effect of LUCAT1 on ferroptosis induction in BC cells. Notably, in an in vivo setting, LUCAT1 emerged as a crucial modulator of ferroptosis inhibition in BC by regulating STAT3 mRNA stability. CONCLUSION: Collectively, our study identifies LUCAT1 as a novel oncogenic player, repressing ferroptosis in BC. These findings shed light on the intricate interplay between lncRNAs and ferroptosis in cancer, implicating LUCAT1 as a promising therapeutic target for patients afflicted with BC. Further investigations into the underlying mechanisms governing LUCAT1-mediated ferroptosis resistance are warranted, with the potential to uncover novel strategies for combating BC progression and improving patient outcomes. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Cao, Yuepeng AU - Cao Y AD - Department of Colorectal Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. Electronic address: MF1535001@smail.nju.edu.cn. FAU - Zou, Zhuo AU - Zou Z AD - Graduate School, Dalian Medical University, Dalian, China. FAU - Wu, Xuhong AU - Wu X AD - Department of Critical Care Medicine, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Li, Weijian AU - Li W AD - Department of Urology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China. FAU - Lu, Zhen AU - Lu Z AD - Department of Anesthesiology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. Electronic address: luzhen120@Sohu.com. FAU - Hu, Jiawei AU - Hu J AD - Department of Endoscopy, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Yang, Liu AU - Yang L AD - Department of Colorectal Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. Electronic address: yangliu@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20231107 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (STAT3 protein, human) RN - 0 (STAT3 Transcription Factor) RN - 0 (long non-coding RNA LUCAT1, human) SB - IM MH - Humans MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - *Ferroptosis/genetics MH - Gene Expression Regulation, Neoplastic MH - In Situ Hybridization, Fluorescence MH - *MicroRNAs/genetics MH - RNA Stability MH - *RNA, Long Noncoding/genetics/metabolism MH - STAT3 Transcription Factor/genetics/metabolism MH - *Urinary Bladder Neoplasms/genetics OTO - NOTNLM OT - Ferroptosis OT - IGF2BP1 OT - LUCAT1 OT - STAT3 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/10 00:44 MHDA- 2024/01/02 11:43 CRDT- 2023/11/09 19:15 PHST- 2023/06/24 00:00 [received] PHST- 2023/10/29 00:00 [revised] PHST- 2023/11/06 00:00 [accepted] PHST- 2024/01/02 11:43 [medline] PHST- 2023/11/10 00:44 [pubmed] PHST- 2023/11/09 19:15 [entrez] AID - S0378-1119(23)00815-6 [pii] AID - 10.1016/j.gene.2023.147974 [doi] PST - ppublish SO - Gene. 2024 Feb 5;894:147974. doi: 10.1016/j.gene.2023.147974. Epub 2023 Nov 7.