MicroRNA-379-5p plays a tumor-suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2

被引:61
作者
Wu, Deyao [1 ,2 ,3 ]
Niu, Xiaobing [1 ,2 ,4 ]
Tao, Jun [1 ,2 ]
Li, Pengchao [1 ,2 ]
Lu, Qiang [1 ,2 ]
Xu, Aiming [1 ,2 ]
Chen, Wei [1 ,2 ]
Wang, Zengjun [1 ,2 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, State Key Lab Reprod Med, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Jiangsu, Peoples R China
[3] Yancheng City 1 Peoples Hosp, Nantong Med Coll, Affiliated Hosp 4, Dept Urol, Yancheng, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Urol, Huaian, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA-379-5p; mouse double minute 2; proliferation; migration; invasion; bladder cancer; CELL-PROLIFERATION; EXPRESSION; P53; SIGNATURES; INVASION; PROTEIN;
D O I
10.3892/or.2017.5607
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:3502 / 3508
页数:7
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