Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

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.

Thymus Gland: A Double Edge Sword for Coronaviruses

“…Therefore, inadequate production or malfunctioning of IFNs favors the existence of the virus in the host. Among various isoforms of INF, INFα has shown antiviral effects against the SARS-CoV virus, whereas INFβ demonstrated an antiviral effect for both SARS and MERS viruses [ 74 ]. The functional relationship between the thymus and different cytokines, including INFs, has shown that thymic cells can initiate the production of cytokines [ 75 ].…”

“…On the other hand, SARS-CoV epitopes of the T and B lymphocytes were thoroughly mapped to analyze the humoral immune responses and the production of different antibodies against a particular virus strain [ 4 ]. It has been observed that the total time needed for a specific antibody to develop and can be detected in the serum was 4 to 14 days [ 74 ]. Additionally, the antibody produced in a long-lasting stage, about two years, is the IgG-neutralizing antibody.…”

Epigenetic modifications in thymic epithelial cells: an evolutionary perspective for thymus atrophy

“…After 17-estradiol (E2) stimulation, the differentially expressed lncRNAs are predicted to be mainly involved in cell cycle and apoptosis in mTECs, like Gm26870 and TCONS_00067179 [ 84 ]. Correspondingly, lncRNAs expression is also widely affected after ovariectomy or orchiectomy, like lnc191945, lnc180466 and lnc186500 [ 85 ]. Taken together, those studies suggest that lncRNA may govern the proliferation of TECs and physiological aging processes by regulating the expression of miRNA or transcription factors.…”

Transcriptome analysis reveals a potential regulatory mechanism of the lnc-5423.6/IGFBP5 axis in the early stages of mouse thymic involution

“…Nevertheless, only a few lncRNAs have functional annotations [14] . In a previous study, we identified 17498 lncRNAs in the mouse thymus and found that 64 lncRNAs might participate in castration-regulated thymic involution through ceRNA [15] . However, the understanding of lncRNAs regulating thymic involution is still not clear.…”