Large-Scale Profiling of lncRNAs in Human Non-Nucleated Cells: Implications in Cell Function and Disease

Abstract

Platelets are blood cells who play critical roles in numerous biological and disease processes. As there are no nuclear DNAs, epigenetic regulation may play more important roles in platelet functions. Recently, long noncoding RNAs (lncRNAs) are proven to be key epigenetic regulators for both mRNAs and proteins in nucleated cells. However, the expression profiles of lncRNAs in non-nucleated cells such as platelets and their functional links are currently completely unknown. In this study, by using large-scale deep sequencing, we determined the expression profiles of lncRNAs in human platelets. We found that 6109 lncRNAs including 1286 novel lncRNAs were indeed expressed in human platelets. Interestingly, 338 lncRNAs were differentially expressed in hyperreactive and hyporeactive platelets, among them, the 6 most abundant and most differentially expressed lncRNAs were further verified by qRT-PCR. By Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and lncRNAs target gene prediction, we found that these aberrantly expressed lncRNAs may be related to platelet activity and other platelet functions. Finally, to provide a proof of concept, we measured the expression levels of ENS0258689, an down-regulated lncRNA in hyperreactive platelets, in platelets from 12 patients with acute myocardial infarction and their aged and sex-matched controls, we found that the LncRNA was strong down-regulated in platelets from patients, which was partially revised by treatment with aspirin a known anti-platelet drug. LnRNAs may represent a novel class of modulators for platelet functions.