Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity.

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-mRNA pairs 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.

journal_name

Blood

journal_title

Blood

authors

Nagalla S,Shaw C,Kong X,Kondkar AA,Edelstein LC,Ma L,Chen J,McKnight GS,López JA,Yang L,Jin Y,Bray MS,Leal SM,Dong JF,Bray PF

doi

10.1182/blood-2010-09-299719

subject

Has Abstract

pub_date

2011-05-12 00:00:00

pages

5189-97

issue

19

eissn

0006-4971

issn

1528-0020

pii

blood-2010-09-299719

journal_volume

117

pub_type

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