KRAS-dependent sorting of miRNA to exosomes
- Vanderbilt University Medical Center, United States
- HudsonAlpha Institute for Biotechnology, United States
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 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 extracellular miRNAs can function in target cells and uncover a potential new mode of action for mutant KRAS in CRC.
Article and author information
Author details
Copyright
© 2015, Cha et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 6,867
- views
-
- 1,791
- downloads
-
- 309
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
KRAS-dependent sorting of miRNA to exosomes
eLife 4:e07197.
https://doi.org/10.7554/eLife.07197
