Abstract
Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. Lately, different pipelines have been developed to identify novel lncRNAs in different diseases, however a little is known about the expression profile and roles of lncRNAs in human subjects developing DVT at high altitude. Methods: In the present study, using RNA sequencing, we compared peripheral blood lncRNA expression profile in human High Altitude deep Vein Thrombosis (HA-DVT) patients with high altitude control and sea level control human subjects. We used DESeq to identify differentially expressed (DE) genes. We identified the noncoding RNAs by annotation database that includes lncRNAs from the NONCODE 3.0 human noncoding RNA database. This was followed by the functional characterization of the identified DE lncRNAs by Co-expressed protein-coding genes analysis. We further performed in silico putative lncRNA-miRNA association study to unravel the endogenous miRNA sponge associated with our candidate lncRNAs. Finally, to validate the in silico findings, siRNA knockdown assay of the candidate LncRNAs was conducted in primary endothelial cells Results: We identified 973 differentially expressed lncRNAs. Co-expressed protein-coding genes analysis resulted in a list of 722 coexpressed protein-coding genes with a Pearson correlation coefficients >0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response and coagulation cascade. Putative lncRNA-miRNA association analysis revealed several miRNAs associated with cardiovascular disorders. Through its miRNA response elements (MREs) to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulates the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. Conclusions: This transcriptome profile describes several potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as biomarker in HA-DVT.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
