Immune System-Related Differentially Expressed Genes, Transcription Factors and microRNAs in Post-Menopausal Females with Osteopenia

Abstract

This study was to identify differentially expressed genes (DEGs) in post-menopausal females with osteopenia and further screened the potentially involved transcription factors (TFs) and microRNAs (miRNAs). Data set GSE13850 of circulating B lymphocytes from post-menopausal females with low or high bone mineral density (BMD) was downloaded from Gene Expression Omnibus. Limma package in R was used to identify DEGs following raw data processing. Enrichment analysis was performed using DAVID (Database for Annotation, Visualization and Integrated Discovery) and visualized using plug-in EnrichmentMap of Cytoscape software. The TFs of DEGs were screened using UCSC (University of California, Santa Cruz) Genome Browser, and miRNAs targeting DEGs were predicted using TarBase, TargetScan and miRecord databases, followed by constructing regulatory networks using Cytoscape software. Totally 52 DEGs were obtained from post-menopausal females with low BMD compared with those with high BMD. Those DEGs including IL-4R, IL-2RG, TGF-β1 and CD74 were mostly related to functions associated with immune response, lymphocyte activation, T cell differentiation, leucocyte activation and immune system process. NFAT, NF-κB and EGR family members might have a regulatory effect on these DEGs. PAX5 could regulate 15 DEGs including ZFP36L2 and KLF13. Abundant miRNAs were also found to target dysregulated ZFP36L2 and KLF13. Dysregulated IL-4R, IL-2RG, TGF-β1 and CD74 may mediate the interplay of immune changes and oestrogen deficiency-induced osteopenia, and disorder functions of NF-κB, NFAT and EGR family members. PAX5 and various miRNAs might exert regulatory effect on osteopenia via targeting ZFP36L2 and KLF13.