Detection of microRNA expression in human peripheral blood microvesicles.
BACKGROUND
MicroRNAs (miRNA) are small non-coding RNAs that regulate translation of mRNA and protein. Loss or enhanced expression of miRNAs is associated with several diseases, including cancer. However, the identification of circulating miRNA in healthy donors is not well characterized. Microvesicles, also known as exosomes or microparticles, circulate in the peripheral blood and can stimulate cellular signaling. In this study, we hypothesized that under normal healthy conditions, microvesicles contain miRNAs, contributing to biological homeostasis.


RESULTS
Microvesicles were isolated from the plasma of normal healthy individuals. RNA was isolated from both the microvesicles and matched mononuclear cells and profiled for 420 known mature miRNAs by real-time PCR. Hierarchical clustering of the data sets indicated significant differences in miRNA expression between peripheral blood mononuclear cells (PBMC) and plasma microvesicles. We observed 71 miRNAs co-expressed between microvesicles and PBMC. Notably, we found 33 and 4 significantly differentially expressed miRNAs in the plasma microvesicles and mononuclear cells, respectively. Prediction of the gene targets and associated biological pathways regulated by the detected miRNAs was performed. The majority of the miRNAs expressed in the microvesicles from the blood were predicted to regulate cellular differentiation of blood cells and metabolic pathways. Interestingly, a select few miRNAs were also predicted to be important modulators of immune function.


CONCLUSIONS
This study is the first to identify and define miRNA expression in circulating plasma microvesicles of normal subjects. The data generated from this study provides a basis for future studies to determine the predictive role of peripheral blood miRNA signatures in human disease and will enable the definition of the biological processes regulated by these miRNA.
Hunter
Melissa Piper
MP
Division of Pulmonary, Allergy, Critical Care, Sleep Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
Ismail
Noura
N
Zhang
Xiaoli
X
Aguda
Baltazar D
BD
Lee
Eun Joo
EJ
Yu
Lianbo
L
Xiao
Tao
T
Schafer
Jeffrey
J
Lee
Mei-Ling Ting
ML
Schmittgen
Thomas D
TD
Nana-Sinkam
S Patrick
SP
Jarjoura
David
D
Marsh
Clay B
CB
D000328:Adult; D000367:Age Factors; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005783:Gender Identity; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged
D035683:MicroRNAs