Breast Cancer-Specific miR Signature Unique to Extracellular Vesicles Includes "microRNA-like" tRNA Fragments.
Extracellular vesicles (EV), including exosomes and shed vesicles, have been implicated in intercellular communication; however, their biomarker potential is less clear. Therefore, EVs derived from MCF7 and MCF10A cells were analyzed to identify unique miRNA (miR) profiles that distinguish their origin. One characteristic common to the miR profiles of MCF7 EVs and their parent cells is the high abundance of miR-21, let-7a, miR-100, and miR-125b, and low levels of miR-205. A second characteristic is the high abundance of "miRNA-like" tRNA fragments, which is unique to the MCF7 EVs, and is not found in comparing the cellular profiles. In addition, correlations were examined in the MCF7 cellular expression levels of these five miRs and two tRNA-derived miRNAs, miR-720 and miR-1274b, and compared with the correlations in MCF7 EV levels. Interestingly, correlations in the cellular expression of miR-125b, miR-100, and let-7a are mirrored in the EVs. In contrast, correlations in tRNA-derived miRNA levels are found only in the EVs. The findings suggest that EV miR clusters can be defined based on functional miR interactions related to correlated cellular expression levels or physical miR interactions, for example, aggregation due to comparable binding affinities to common targets.


CONCLUSIONS
These results point to using high levels of tRNA-derived small RNA fragments in combination with known miR signatures of tumors to distinguish tumor-derived EVs in circulation from EVs derived from other cell sources. Such biomarkers would be unique to the EVs where high abundances of tRNA fragments are amplified with respect to their cellular levels.
William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio. Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, The Ohio State University, Columbus, Ohio.
Nicole
N
Guzman
Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, The Ohio State University, Columbus, Ohio. Department of Chemistry, The Ohio State University, Columbus, Ohio.
Kitty
K
Agarwal
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas.
Dilip
D
Asthagiri
Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio.
Lianbo
L
Yu
Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio.
Motoyasu
M
Saji
Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio.
Matthew D
MD
Ringel
William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio. Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, The Ohio State University, Columbus, Ohio. paulaitis.1@osu.edu.
Michael E
ME
Paulaitis
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000067128:Extracellular Vesicles / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism
D035683:MicroRNAs; D012343:RNA, Transfer