Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity

Srikanth Nagalla, Chad Shaw, Xianguo Kong, Altaf A. Kondkar, Leonard C. Edelstein, Lin Ma, Junmei Chen, G. Stanley McKnight, José A. López, Linghai Yang, Ying Jin, Molly S. Bray, Suzanne M. Leal, Jing Fei Dong, Paul F. Bray

Research output: Contribution to journalArticle

206 Scopus citations

Abstract

MicroRNAs (miRNAs) regulate cell physiology by altering protein expression, but the biology of platelet miRNAs is largely unexplored. We tested whether platelet miRNA levels were associated with platelet reactivity by genome-wide profiling using platelet RNA from 19 healthy subjects. We found that human platelets express 284 miRNAs. Unsupervised hierarchical clustering of miRNA profiles resulted in 2 groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed (DE) between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. Using whole genome mRNA expression data on these same subjects, we computationally generated a high-priority list of miRNA-mRNApairs in which the DE platelet miRNAs had binding sites in 3′-untranslated regions of DE mRNAs, and the levels were negatively correlated. Three miRNA-mRNA pairs (miR-200b: PRKAR2B, miR-495:KLHL5, and miR-107: CLOCK) were selected from this list, and all 3 miRNAs knocked down protein expression from the target mRNA. Reduced activation from platelets lacking PRKAR2B supported these findings. In summary, (1) platelet miRNAs are able to repress expression of platelet proteins, (2) miRNA profiles are associated with and may predict platelet reactivity, and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets.

Original languageEnglish (US)
Pages (from-to)5189-5197
Number of pages9
JournalBlood
Volume117
Issue number19
DOIs
StatePublished - May 12 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Nagalla, S., Shaw, C., Kong, X., Kondkar, A. A., Edelstein, L. C., Ma, L., Chen, J., McKnight, G. S., López, J. A., Yang, L., Jin, Y., Bray, M. S., Leal, S. M., Dong, J. F., & Bray, P. F. (2011). Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood, 117(19), 5189-5197. https://doi.org/10.1182/blood-2010-09-299719