Wu Deyao, Niu Xiaobing, Tao Jun, Li Pengchao, Lu Qiang, Xu Aiming, Chen Wei, Wang Zengjun
State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
Oncol Rep. 2017 Jun;37(6):3502-3508. doi: 10.3892/or.2017.5607. Epub 2017 Apr 27.
Bladder cancer is the second most common urological malignancy in the US and is the most frequently diagnosed urological malignancy in China. An increasing amount of evidence indicates that microRNAs perform extremely important functions in many biological processes related to the formation and progression of cancers, including bladder cancer. Previous studies have reported that microRNA‑379-5p (miR-379-5p) is involved in tumour initiation and development in human cancers. However, the expression pattern, biological functions and the underlying mechanisms of miR-379-5p in bladder cancer remain unknown. The present study demonstrated that the expression levels of miR‑379-5p in bladder cancer tissues and cell lines were lower than the levels in adjacent normal tissues and the human bladder epithelial immortalized SV-HUC-1 cell line. Restoration of the expression of miR-379-5p inhibited bladder cancer cell proliferation, migration and invasion. Mouse double minute 2 (MDM2) was identified as a direct target gene of miR-379-5p. Furthermore, similar to miR-379-5p overexpression in bladder cancer cells, inhibition of MDM2 exerted tumor-suppressive effects. Rescue experiments showed that upregulation of MDM2 reversed the inhibitory effects of miR-379-5p on bladder cancer cell proliferation, migration and invasion. MDM2 was highly expressed and inversely correlated with miR-379-5p expression in bladder cancer tissues. These findings suggest that the miR-379-5p/MDM2 pathway plays an important role in bladder cancer and could serve as a potential candidate for bladder cancer therapeutics.
膀胱癌是美国第二常见的泌尿系统恶性肿瘤,在中国则是最常被诊断出的泌尿系统恶性肿瘤。越来越多的证据表明,微小RNA在包括膀胱癌在内的许多与癌症形成和进展相关的生物学过程中发挥着极其重要的作用。先前的研究报道,微小RNA-379-5p(miR-379-5p)参与人类癌症的肿瘤发生和发展。然而,miR-379-5p在膀胱癌中的表达模式、生物学功能及潜在机制仍不清楚。本研究表明,miR-379-5p在膀胱癌组织和细胞系中的表达水平低于相邻正常组织及人膀胱上皮永生化SV-HUC-1细胞系中的水平。miR-379-5p表达的恢复抑制了膀胱癌细胞的增殖、迁移和侵袭。小鼠双微体2(MDM2)被鉴定为miR-379-5p的直接靶基因。此外,与miR-379-5p在膀胱癌细胞中的过表达类似,抑制MDM2也发挥了肿瘤抑制作用。挽救实验表明,上调MDM2可逆转miR-379-5p对膀胱癌细胞增殖、迁移和侵袭的抑制作用。MDM2在膀胱癌组织中高表达,且与miR-379-5p的表达呈负相关。这些发现表明,miR-379-5p/MDM2通路在膀胱癌中起重要作用,可能成为膀胱癌治疗的潜在候选靶点。