Talk abstracts

Talk on Saturday 11:10-11:25am submitted by Sree C. Ganapathiraju

MicroRNAs Released From Cells Differ From the Cellular miRNA Population

Lucy Pigati (Department of Pathology, The Chicago Medical School, Rosalind Franklin University), Sree C. Ganapathiraju (Department of Cell Biology and Anatomy, The Chicago Medical School, Rosalind Franklin University), Michelle Hastings (Department of Cell Biology and Anatomy, The Chicago Medical School, Rosalind Franklin University), Steven Hearn (Cold Spring Harbor Laboratory Microscopy Facility, Cold Spring Harbor Laboratory), David Danforth (Surgery Branch, CCR, NCI, NIH), Dominik Duelli (Department of Pathology, The Chicago Medical School, Rosalind Franklin University)

Abstract:
A major challenge in the fight against cancer, including breast cancer, is early and sensitive detection of neoplasms. Some miRNAs with diagnostic value found in cancer cells have also been detected in body fluids. Thus, circulating miRNAs may afford diagnosis with low invasiveness. However, it remains to be determined, if the released miRNA population is the same as the miRNA population retained by the cell. We find that individual miRNA species are released from cells at different rates. This rate is constant for most miRNAs. Importantly, miRNAs with diagnostic value in breast cancer, such as miR-451, are primarily released into the environment, whereas miR-16, a common cellular miRNA, is mostly retained in the cell. These results suggest that miRNAs are released selectively. In part, this selection may be explained by reports that miRNAs are released from cells still tethered to their mRNA target. However, we find that for some miRNAs, including miR-16 and miR-21, both mature and immature miRNAs are released by cells, whereas only mature miR-451 is released by cells, suggesting that alternative pathways exist. Furthermore, about half of the analyzed mature miRNAs that are released differ from the cell-retained population in size, suggesting that additional processing mechanisms occur during the release of these miRNAs. Some of these miRNA properties can also be detected in human milk and ductal lavages, which contain products of mammary epithelia. This suggests physiological relevance of the observed differences in the released miRNA population. Finally, we find that miRNAs are released from cells in several different nano-vesicles, including exosomes, apoptotic bodies and smaller components. These findings indicate the presence of one or more selection and processing mechanisms in the release of miRNAs. In addition, these data imply that the diagnostic profiles of released miRNAs are expected to be different than the cellular miRNA profile.

Keywords: circulating microRNAs, transport, cancer diagnostics