线粒体核糖核酸加工内切核糖核酸酶的外泌体长非编码核糖核酸核糖核酸酶成分被定义为膀胱癌的潜在非侵入性诊断生物标志物,并通过 miR-206/G6PD 轴促进肿瘤发生。
Exosomal Long Non-Coding Ribonucleic Acid Ribonuclease Component of Mitochondrial Ribonucleic Acid Processing Endoribonuclease Is Defined as a Potential Non-Invasive Diagnostic Biomarker for Bladder Cancer and Facilitates Tumorigenesis via the miR-206/G6PD Axis.
发表日期:2023 Nov 06
作者:
Yuting Gao, Xuan Wang, Huarong Luo, Chen Chen, Jing Li, Ruixin Sun, Dong Li, Zujun Sun
来源:
Cancers
摘要:
膀胱癌(BLCA)是对有助于早期诊断的特定非侵入性肿瘤生物标志物高度敏感的癌症之一。外泌体衍生的长非编码 RNA (lncRNA) 有希望作为 BLCA 的诊断生物标志物。在这项研究中,我们采用 RNA 测序来比较三名 BLCA 患者和三名健康个体尿液外泌体中 lncRNA 的表达模式。 RMRP 显示出最显着的差异表达。与健康个体相比,BLCA 患者的尿液和血浆外泌体中 RMRP 表达水平升高。 RMRP 与某些 BLCA 患者的临床病理特征(包括肿瘤分期、不良预后和肿瘤分级)显着相关。使用尿液和血浆外泌体中的 RMRP 进行联合诊断,通过接受者操作特征曲线分析证明了卓越的诊断性能。研究发现 RMRP 在体外和体内均与 BLCA 肿瘤进展以及通过 miR-206/G6PD 轴的细胞迁移和侵袭过程相关。从机制上讲,RMRP 作为 miR-206 海绵,正如双荧光素酶报告基因检测和 RNA 免疫沉淀所表明的那样。我们的研究表明,尿液和血浆外泌体中 RMRP 的联合诊断可以作为 BLCA 患者优异的非侵入性诊断生物标志物。此外,靶向 RMRP/miR-206/G6PD 轴有望成为 BLCA 的治疗策略。
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.