Bladder cancer (BLCA) is one of the cancers that is highly sensitive to specific non-invasive tumor biomarkers that facilitate early diagnosis. Exosome-derived long non-coding RNAs (lncRNAs) hold promise as diagnostic biomarkers for BLCA. In this study, we employed RNA-sequencing to compare the expression patterns of lncRNAs in urine exosomes from three BLCA patients and three healthy individuals. RMRP displayed the most significant differential expression. Elevated RMRP expression levels were observed in urinary and plasma exosomes from BLCA patients compared with those from healthy individuals. RMRP exhibited significant associations with certain BLCA patient clinicopathological features, including tumor stage, poor prognosis, and tumor grade. Combined diagnosis using RMRP in urine and plasma exosomes demonstrated a superior diagnostic performance with receiver operating characteristic curve analysis. RMRP was found to be related to BLCA tumor progression and the cell migration and invasion processes via the miR-206/G6PD axis both in vitro and in vivo. Mechanistically, RMRP serves as an miR-206 sponge, as suggested by dual-luciferase reporter assays and RNA immunoprecipitation. Our study suggests that the combined diagnosis of RMRP in urinary and plasma exosomes can serve as an excellent non-invasive diagnostic biomarker for BLCA patients. Additionally, targeting the RMRP/miR-206/G6PD axis holds promise as a therapeutic strategy for BLCA.
膀胱癌(BLCA)是对特定非侵入性肿瘤生物标志物高度敏感的癌症之一,这些标志物有助于早期诊断。外泌体来源的长链非编码RNA(lncRNA)有望成为BLCA的诊断生物标志物。本研究通过RNA测序技术,比较了三名BLCA患者与三名健康个体尿液外泌体中lncRNA的表达模式。结果显示RMRP的表达差异最为显著。与健康个体相比,BLCA患者尿液及血浆外泌体中RMRP表达水平显著升高。RMRP表达与BLCA患者部分临床病理特征(包括肿瘤分期、不良预后及肿瘤分级)存在显著相关性。联合检测尿液和血浆外泌体中的RMRP,通过受试者工作特征曲线分析显示出更优的诊断效能。体内外实验表明,RMRP通过miR-206/G6PD轴参与BLCA肿瘤进展及细胞迁移侵袭过程。机制上,双荧光素酶报告基因实验和RNA免疫沉淀实验证实RMRP可作为miR-206的分子海绵。本研究表明,联合检测尿液和血浆外泌体中的RMRP可作为BLCA患者优异的非侵入性诊断生物标志物,同时靶向RMRP/miR-206/G6PD轴有望成为BLCA的治疗策略。