Exosome-transmitted microRNA-133b inhibited bladder cancer proliferation by upregulating dual-specificity protein phosphatase 1

被引:43
作者
Cai, Xiaoxiao [1 ]
Qu, Lili [1 ]
Yang, Jian [2 ]
Xu, Junwen [1 ]
Sun, Li [1 ]
Wei, Xiaowei [1 ]
Qu, Xiaojun [1 ]
Bai, Tingting [3 ]
Guo, Zhirui [3 ]
Zhu, Yefei [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 2, Lab Med Ctr, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 2, Urinary Surg, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Affiliated Hosp 2, Gerontol Ctr, Nanjing, Jiangsu, Peoples R China
来源
CANCER MEDICINE | 2020年 / 9卷 / 16期
关键词
Bladder cancer; Dual-specificity protein phosphatase 1; Exosome; microRNA-133b; Proliferation; MESENCHYMAL STEM-CELLS; EXPRESSION; CARCINOMA; DUSP1; PROGRESSION; STRESS; KINASE;
D O I
10.1002/cam4.3263
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bladder Cancer (BC) is the ninth most common tumor in the world and one of the most common malignant tumors of the urinary system. Some studies reported that miR-133b expression is reduced in BC, but whether it plays a role in the development of BC and its mechanism is unclear. microRNAs can be packaged into exosomes to mediate communication between tumor cells, affecting their proliferation and apoptosis. The objective of this study was to investigate the effect of exosomal miR-133b on BC proliferation and its molecular mechanism. Firstly, the expression of miR-133b was evaluated in BC and adjacent normal tissues, as well as in serum exosomes of BC patients and healthy controls. Then the delivery and internalization of exosomes in cells was observed through fluorescence localization. Cell viability and apoptosis were assessed in BC cells transfected with mimics and incubated with exosomes. The role of exosomal miR-133b was also analyzed in nude mice transplant tumors. Furthermore, the target gene of miR-133b was predicted through bioinformatics. The level of miR-133b was significantly decreased in BC tissues and in exosomes from serum of patients, which was correlated with poor overall survival in TCGA. Exosomal miR-133b could be obtained using BC cells after transfection with miR-133b mimics. The miR-133b expression increased after incubation with exosomal miR-133b, which lead to the inhibition of viability and increase of apoptosis in BC cells. Exosomal miR-133b could suppress tumor growth in vivo. In addition, we found that exosomal miR-133b may play a role in suppressing BC proliferation by upregulating dual-specificity protein phosphatase 1 (DUSP1). These findings may offer promise for new therapeutic directions of BC.
引用
收藏
页码:6009 / 6019
页数:11
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