Exosomal lncRNA CIAT1 promotes collective invasion of bladder cancer
10.3969/j.issn.1006-5725.2025.09.005
- VernacularTitle:外泌体lncRNA CIAT1促进膀胱癌集体侵袭的机制
- Author:
Zhicong LIU
1
;
Daiyin LIU
;
Juntian LONG
;
Chixing CHENG
;
Jian HUANG
Author Information
1. 中山大学孙逸仙纪念医院泌尿外科(广东 广州 510030);广东省恶性肿瘤表观遗传与基因调控重点实验室(广东 广州 510030)
- Publication Type:Journal Article
- Keywords:
bladder cancer;
exosomes;
lncRNA;
collective invasion
- From:
The Journal of Practical Medicine
2025;41(9):1299-1308
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and molecular mechanisms of bladder cancer-derived exosomal long non-coding RNA(lncRNA)CIAT1 in mediating collective invasion and to evaluate its clinical significance and potential therapeutic value.Methods High-throughput sequencing was used to identify lncRNAs that are highly expressed in exosomes from bladder cancer and lymph node metastatic tissues.CIAT1 was selected for further validation in clinical bladder cancer samples.By constructing CIAT1-overexpressing and knockdown bladder cancer cells,we demonstrated in vitro that CIAT1-contained exosomes target cancer-associated fibroblasts(CAFs)to induce collective invasion.The underlying mechanism of CIAT1 in bladder cancer collective invasion was explored through RNA pull-down,RNA immunoprecipitation(RIP),dual-luciferase reporter assays,chromatin isolation by RNA purification(ChIRP)and chromatin immunoprecipitation(ChIP).Results CIAT1 was significantly upregulated in exosomes derived from bladder cancer tissues compared to adjacent normal tissues by High-throughput sequencing(fold change>1.5,P<0.05)and clinical sample validation(P<0.01).In vitro experiments,exosomal CIAT1 was selectively internalized by cancer-associated fibroblasts(CAFs),significantly enhancing collective invasion of bladder cancer via regulating CAFs.In co-culture models,CIAT1 overexpression group showed increased total number and total length of collective invasion chains compared to the control group(P<0.01 for both).Mechanistically,CIAT1 was packaged into exosomes via binding to hnRNPA2B1,and internalized by CAFs,where it activated N-cadherin transcription by modulating H3K4me3 histone modification at the N-cadherin promoter.Consistently,the CIAT1 overexpression group exhibited elevated collective invasion chain numbers and lengths compared to the control group(P<0.01 for both).However,blocking N-cadherin reversed the pro-invasive effects of CIAT1,with no significant differences in chain numbers or lengths between the CIAT1 overexpression+N-cadherin blockade group and controls(P>0.05 for both).Further clinical correlation analysis confirmed that CIAT1-regulated N-cadherin is closely associated with collective invasion in bladder cancer patients(P<0.01).Conclusions Exosomal CIAT1 derived from bladder cancer cells targets CAFs to activate N-cadherin transcription,thereby promoting bladder cancer collective invasion.
