KRAS-dependent sorting of miRNA to exosomes

被引：331

作者：

Cha, Diana J. ^{[1
,2
]}

Franklin, Jeffrey L. ^{[3
,4
,5
]}

Dou, Yongchao ^{[6
]}

Liu, Qi ^{[6
]}

Higginbotham, James N. ^{[3
,4
]}

Beckler, Michelle Demory ^{[4
]}

Weaver, Alissa M. ^{[3
,7
,8
]}

Vickers, Kasey ^{[9
]}

Prasad, Nirpesh ^{[10
]}

Levy, Shawn ^{[10
]}

Zhang, Bing ^{[6
]}

Coffey, Robert J. ^{[3
,4
,5
]}

Patton, James G. ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Dept Biol Sci, Nashville, TN USA

[2] Vanderbilt Univ, Nashville, TN 37235 USA

[3] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37235 USA

[4] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[5] Affairs Med Ctr, Nashville, TN USA

[6] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA

[7] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN USA

[8] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA

[9] Vanderbilt Univ, Med Ctr, Dept Cardiol, Nashville, TN USA

[10] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

来源：

ELIFE | 2015年 / 4卷

基金：

美国国家卫生研究院;

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; PROSTATE-CANCER CELLS; MICRORNA BIOGENESIS; MESSENGER-RNAS; MIR-100; GROWTH; MECHANISM; MIRBASE; STEM; SEQ;

D O I：

10.7554/eLife.07197

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

Mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. To test whether exosomal RNAs also contribute to changes in gene expression in recipient cells, and whether mutant KRAS might regulate the composition of secreted microRNAs (miRNAs), we compared small RNAs of cells and matched exosomes from isogenic CRC cell lines differing only in KRAS status. We show that exosomal profiles are distinct from cellular profiles, and mutant exosomes cluster separately from wild-type KRAS exosomes. miR-10b was selectively increased in wild-type exosomes, while miR-100 was increased in mutant exosomes. Neutral sphingomyelinase inhibition caused accumulation of miR-100 only in mutant cells, suggesting KRAS-dependent miRNA export. In Transwell co-culture experiments, mutant donor cells conferred miR-100-mediated target repression in wild-type-recipient cells. These findings suggest that extracellular miRNAs can function in target cells and uncover a potential new mode of action for mutant KRAS in CRC.

引用

页数：22

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