MicroRNA-214 Suppresses Oncogenesis and Exerts Impact on Prognosis by Targeting PDRG1 in Bladder Cancer

MicroRNA-214 (miR-214) has been reported to be dysregulated in human bladder cancer tissues. We aimed to investigate the clinical correlation, biological significance and molecular network of miR-214 in bladder cancer. Our results showed miR-214 was down-regulated in bladder cancer tissues and significantly associated with tumor stage, lymph node status, grade, multifocality, history of non-muscle-invasive bladder cancer (NMIBC). Moreover, miR-214 could serve as an independent factor of recurrence-free survival (RFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC). Restoration of miR-214 expression in bladder cancer cell lines inhibited cell proliferation, migration, invasion and markedly promoted apoptosis. Dual-luciferase reporter assay recognized PDRG1 as direct downstream target gene of miR-214. PDRG1 was significantly increased in tumors low of miR-214 and knockdown of PDRG1 mimicked the effects of miR-214 overexpression. Our findings manifest that miR-214 could exert tumor-suppressive effects in bladder cancer by directly down-regulating oncogene PDRG1 and suggest an appealing novel indicator for prognostic and therapeutic intervention of bladder cancer.

已有研究表明，微小RNA-214（MicroRNA-214，简称miR-214）在人类膀胱癌组织中存在表达失调现象。本研究旨在探讨miR-214在膀胱癌中的临床相关性、生物学意义及分子调控网络。研究结果显示，miR-214在膀胱癌组织中呈低表达状态，且与肿瘤分期、淋巴结状态、病理分级、多灶性以及非肌层浸润性膀胱癌（non-muscle-invasive bladder cancer，简称NMIBC）病史显著相关。此外，对于肌层浸润性膀胱癌（muscle-invasive bladder cancer，简称MIBC）患者，miR-214可作为无复发生存期（recurrence-free survival，简称RFS）与总生存期（overall survival，简称OS）的独立预测因子。在膀胱癌细胞系中恢复miR-214的表达，可抑制细胞增殖、迁移与侵袭能力，并显著促进细胞凋亡。双荧光素酶报告基因实验证实，PDRG1是miR-214的直接下游靶基因。在miR-214低表达的肿瘤组织中，PDRG1的表达水平显著升高；敲低PDRG1可模拟miR-214过表达所产生的生物学效应。本研究结果表明，miR-214可通过直接下调癌基因PDRG1的表达，在膀胱癌中发挥抑癌作用，同时提示其可作为膀胱癌预后评估与治疗干预的潜在新型标志物。