Microarray Profiling and Co-Expression Analysis of Long Noncoding RNA and Apoptosis-Associated mRNA in Mouse Intestinal Mucosa Following IntestinalI schemia/Reperfusion Injury / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】To investigate the lncRNA expression profile and potential roles in mouse intestinal mucosa after I/R treatment and explore the co-expression relationship between dysregulated lncRNA and apoptotic mRNA at the early stage of reperfusion. 【Methods】 The expression profiles of lncRNA were obtained using microarray and some lncRNA were further validated by quantitative real- time polymerase chain reaction （qRT- PCR）. Gene ontology（GO）analyses were performed to determine closely related biological functions，especially apoptosis-related functions. Finally， the known apoptosis- related mRNA with obviously changes were selected to construct the co-expression network of the dysregulated lncRNA and their correlated apoptotic mRNA， and were analyzed by CNC analysis to calculate the significant correlation of IncRNA-mRNA pairs.【Results】Compared with sham operation group，the expression profile of lncRNA in intestinal epithelium of mice after intestinal I/R was significantly changed ，including 1 503 up- regulated lncRNAs and 2 099 down- regulated lncRNA （Fold change≥2，P<0.05）. At the same time，1 528 mRNA were up- regulated in I/R group，while 1 630 mRNA were down- regulated（fold change≥2.0，P<0.05）. GO enrichment analysis showed that the main functions involved in regulation were lipid metabolism，redox reaction，stress reaction，apoptosis process，programmed cell death，cell cycle，inflammatory response，endothelial cell differentiation and proliferation， tissue remodeling，MAPK，Wnt，vascular endothelial growth factor signaling pathway and so on. Apoptosis-related subitems were enriched in the up- and down-regulated annotations of GO molecular function in different forms ，which were in the forefront. There was a significant co-expression relationship between apoptosis- related mRNA and dysregulated lncRNA. 【Conclusion】 In this study，we established and preliminarily validated the expression profiles of the differentially expressed lncRNA at the early stage of reperfusion in mouse intestinal ischemia injury. Bioinformatics analysis showed that the important biological function of dysregulated lncRNA was the regulation of apoptosis-related processes，and a large number of those lncRNA were indeed highly coexpressed with apoptotic genes ，which would provide a basis and direction for future research.