TY - JOUR
T1 - Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity
AU - Nagalla, Srikanth
AU - Shaw, Chad
AU - Kong, Xianguo
AU - Kondkar, Altaf A.
AU - Edelstein, Leonard C.
AU - Ma, Lin
AU - Chen, Junmei
AU - McKnight, G. Stanley
AU - López, José A.
AU - Yang, Linghai
AU - Jin, Ying
AU - Bray, Molly S.
AU - Leal, Suzanne M.
AU - Dong, Jing Fei
AU - Bray, Paul F.
PY - 2011/5/12
Y1 - 2011/5/12
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2010-09-299719
DO - 10.1182/blood-2010-09-299719
M3 - Article
C2 - 21415270
AN - SCOPUS:79955948510
SN - 0006-4971
VL - 117
SP - 5189
EP - 5197
JO - Blood
JF - Blood
IS - 19
ER -