Vanderbilt Summer Science Academy

KRAS-dependent sorting of long RNAs into exosomes

Recent evidence suggests that the secreted contents of exosomes may be selectively loaded based on cellular status. The mechanism of exosomal secretion and uptake between these cells is of interest due to its possible role in tumor development, progression, and metastasis. We have previously shown that mutant KRAS, a primary driver of tumor progression, drives the release of exosomes with distinct macromolecular (protein, small RNAs) makeup in a colorectal cancer (CRC) cell model. To test whether KRAS mutations regulated the loading of long RNAs (like lncRNAS or mRNAs), we profiled RNAs of cells and exosomes of isogenically matched CRC cell lines differing only in KRAS status. Further, using co-culturing experiments, we tested whether full length mRNAs, specifically Rab13, are functionally trafficked from donor to recipient cells through extracellular delivery. Collectively, this suggests that full length RNAs may play a role in cell-to-cell signaling through exosomal delivery, advancing our understanding of exRNA biology in CRC and facilitating the development of potential exRNA biomarkers.