Genome-wide analysis of differentially expressed long noncoding RNAs induced by low shear stress in human umbilical vein endothelial cells

Abstract

Abnormal shear stress plays a critical role in development of atherosclerosis via modulating complex signal pathways. Long noncoding RNAs (lncRNAs) function directly as RNAs. However, the differential expression of lncRNAs and their net-work regulating the cellular response to the change of shear stress remains to be unclear. Human umbilical vein endothelial cells (HUVEC) were exposure to lower shear stress (2 dynes/cm 2 ) for 120 minutes. Differential expression (defined as a fold change ≥2.0, P<0.05) of lncRNAs and mRNAs was obtained by microarray and analyzed by Box- and Scatter-plot, Heat Map and Hierarchical Clustering. Gene ontology and pathway analyses were performed thereafter. Of 149 lncRNAs differentially expressed between sheared and normal emdothelial cells, 64 lncRNAs were upregulated and 85 lncRNAs were downregulated. 109 mRNAs were differentially expressed (upregulated and 30 downregulated). We found 84 matched lncRNAmRNA pairs for 62 differentially expressed lncRNAs and 35 differentially expressed mRNAs. 9 pathways through which low shear stress acted on the regulation of cellular function were identified. According to pathway analysis, two up-stream genes (TLR4 and BDNF) were upregulated. Our study provides the expression profiles of lncRNA and mRNA in sheared cells (after 120 min), and reports that TLR4 and BDNF pathways plays crucial role in low shear stress-induced cellular injury, among 84 paired differentially expressed lncRNA-mRNA.