KRAS-dependent sorting of miRNA to exosomes.

Abstract:

: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.

journal_name

Elife

journal_title

eLife

authors

Cha DJ,Franklin JL,Dou Y,Liu Q,Higginbotham JN,Demory Beckler M,Weaver AM,Vickers K,Prasad N,Levy S,Zhang B,Coffey RJ,Patton JG

doi

10.7554/eLife.07197

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

e07197

issn

2050-084X

journal_volume

4

pub_type

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