Dissertation/Thesis Abstract

The author has requested that access to this graduate work be delayed until 2019-08-13. After this date, this graduate work will be available on an open access basis.
KRAS-Dependent Regulation of Extracellular RNAs in Colorectal Cancer
by Cha, Diana Jean, Ph.D., Vanderbilt University, 2017, 133; 13834977
Abstract (Summary)

Mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. To test whether exosomal RNA might also contribute to changes in gene expression in recipient cells, and to test 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 KRAS exosomes cluster separately from wild type KRAS exosomes. miR-10b was selectively increased in wild type KRAS exosomes while miR-100 was increased in mutant KRAS exosomes. Neutral sphingomyelinase inhibition caused accumulation of miR-100 only in mutant KRAS cells, suggesting KRAS-dependent miRNA export. In Transwell co-culture experiments, mutant KRAS donor cells conferred miR-100 -mediated target repression in wild type KRAS 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.

Indexing (document details)
Advisor: Graham, Todd R.
Commitee: Coffey, Robert, Graham, Todd, Patton, james G., Rokas, Antonis, Vickers, Kasey
School: Vanderbilt University
Department: Biological Sciences
School Location: United States -- Tennessee
Source: DAI-B 80/06(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biology, Molecular biology, Cellular biology
Keywords: Colon cancer, ExRNA, Exosomes, KRAS, miRNA
Publication Number: 13834977
ISBN: 9780438820685
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