Comprehensive Analysis of lncRNA and Gene Expression Profiles during the Early Stages of Mice Thymic Involution

Age-related thymic involution is one of the significant reasons for induced immunity decline. Recent evidence indicated that long non-coding RNAs (lncRNAs) are widely involved in regulating organ development. Thymus volume reached the maximum at 1-month-old, then it gradually involuted and adipocytes deposited with age. Our previous studies have found that castration can regulate the expression of non-coding RNA in thymus. However, the RNAs' expression profiles in early stages of mice thymic involution have not been reported. In this study, we collected mice thymus at the age of 1 month, 3 months, and 6 months for sequencing to observe the lncRNA and gene expression profiles in the early stage of thymic involution. RNA sequencing showed that 340 and 152 differentially expressed genes (DEGs) were identified during the development stage (1-month-old) and involution stages (3-month-old and 6-month-old) in males and females, respectively. GO analysis showed that DEGs were significantly enriched in immune response activation, cell proliferation, and fatty acid metabolic process, etc. Next, we screened 16 key DEGs co-expressed by males and females based on the STRING database for further analysis. Meanwhile, we identified 29 differentially expressed lncRNAs (DELs) with the same expression trend during thymus development and involution stage in males and females. Then we predicted the targeting relationship between those above 16 key DEGs and miRNAs, and the miRNAs related to the 29 DELs mentioned above. Finally, we successfully constructed a novel lncRNA–miRNA–mRNA network related to adipocyte deposition using Cytoscape. In summary, this study systematically identified and analyzed the expression profiles of lncRNAs and genes during the early stages of thymic involution for the first time, which provided a valuable reference for further exploring the roles of lncRNAs in thymic involution.