Abstract
Thymic degeneration and regeneration are regulated by estrogen and androgen. Recent studies have found that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in organ development. In this study, RNA sequencing (RNA-seq) results showed that ovariectomy significantly affected 333 lncRNAs, 51 miRNAs, and 144 mRNAs levels (p < 0.05 and |log2fold change| > 1), and orchiectomy significantly affected 165 lncRNAs, 165 miRNAs, and 208 mRNA levels in the thymus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) were closely related to cell development and immunity. Next, we constructed two lncRNA–miRNA–mRNA networks using Cytoscape based on the targeting relationship between differentially expressed miRNAs (DEMs) and DEGs and differentially expressed lncRNAs (DELs) analyzed by TargetScan and miRanda. Besides, we screened DEGs that were significantly enriched in GO and in ceRNA networks to verify their expression in thymocytes and thymic epithelial cells (TECs). In addition, we analyzed the promoter sequences of DEGs, and identified 25 causal transcription factors. Finally, we constructed transcription factor-miRNA-joint target gene networks. In conclusion, this study reveals the effects of estrogen and androgen on the expression of miRNAs, lncRNAs, and mRNAs in mice thymus, providing new insights into the regulation of thymic development by gonadal hormones and non-coding RNAs.
Highlights
As a primary immune organ, the thymus regulates adaptive immunity by producing naïve T lymphocytes [1]
Venny analysis showed that 13,343 long non-coding RNAs (lncRNAs), 878 miRNAs, and 37,643 mRNAs were expressed in all groups, accounting for 76.3%, 57.5%, and 80.8% of the total readings, respectively (Figure 2a–c)
The results showed that 416 that 416 lncRNAs, 68 miRNAs, and 225 mRNAs were remarkably differentially expressed after lncRNAs, miRNAs, and 225 mRNAs were remarkably differentially expressed ovariectomy ovariectomy and orchiectomy
Summary
As a primary immune organ, the thymus regulates adaptive immunity by producing naïve T lymphocytes [1]. Thymus degeneration is closely related to age, and the main age-related manifestations are thymus size becomes smaller, reduced thymic epithelial cells, and gradually decreased naive T lymphocyte output [2,3]. When naive T lymphocytes in the peripheral circulation system decrease with aging, effector-memory T lymphocytes will proliferate to maintain a constant number of total lymphocytes [4,5,6]. The reactivity of old lymphocytes to new infections is weak. The reduction in the number of naïve T lymphocytes is considered to be one of the causes of the decline in resistance to infections and cancer in older adults [7,8]. Gui found that the number of thymocytes in female and male mice decreased sharply at 3 months of age [9]
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