MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression

被引：414

作者：

Teng, Yun ^{[1
]}

Ren, Yi ^{[2
]}

Hu, Xin ^{[3
,4
]}

Mu, Jingyao ^{[1
]}

Samykutty, Abhilash ^{[1
]}

Zhuang, Xiaoying ^{[1
]}

Deng, Zhongbin ^{[1
]}

Kumar, Anil ^{[1
]}

Zhang, Lifeng ^{[1
]}

Merchant, Michael L. ^{[5
,6
]}

Yan, Jun ^{[1
]}

Miller, Donald M. ^{[1
]}

Zhang, Huang-Ge ^{[1
,7
]}

机构：

[1] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA

[2] Huaian First Peoples Hosp, Dept Breast & Thyroid Surg, Huaian 223001, Jiangsu, Peoples R China

[3] Univ Texas Houston, Grad Sch Biomed Sci, Program Biostat Bioinformat & Syst Biol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[5] Univ Louisville, Kidney Dis Program, Louisville, KY 40292 USA

[6] Univ Louisville, Clin Prote Ctr, Louisville, KY 40292 USA

[7] Robley Rex VA Med Ctr, Louisville, KY 40206 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院;

关键词：

MAJOR VAULT PROTEIN; EXTRACELLULAR VESICLES; DRUG-RESISTANCE; TUMOR-GROWTH; RNA; COMMUNICATION; BIOMARKERS; MICRORNA; MICROENVIRONMENT; METASTASIS;

D O I：

10.1038/ncomms14448

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP). Knockout of MVP leads to miR-193a accumulation in the exosomal donor cells instead of exosomes, inhibiting tumour progression. Furthermore, miR-193a causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1, which upregulates Ccnd2 and c-Myc. Human colon cancer patients with more advanced disease show higher levels of circulating exosomal miR-193a. In summary, our data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression.

引用

页数：16

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