Identification of key genes and miRNA-mRNA regulatory networks associated with bone marrow immune microenvironment regulations in multiple myeloma by integrative bioinformatics analysis

The deregulation of microRNAs (miRNAs) and genes in the bone marrow microenvironment have been involved with the pathogenesis of multiple myeloma (MM). However, the exploration of miRNA-mRNA regulatory networks in MM remains lacking. We used GSE125363, GSE125361, GSE47552, GSE2658, GSE136324, GSE16558, and GSE13591 datasets for this bioinformatics study. We identified 156 downregulated and 13 upregulated differentially expressed miRNAs (DEmiRs) in MM. The DEmiRs are associated with the enrichment of pathways mainly involved with cancers, cellular signaling, and immune regulations. We identified 112 hub genes associated with five significant clusters in MM. Moreover, we identified 9 upregulated hub genes (such as <i>IGF1, RPS28, UBA52, CDKN1A,</i> and <i>CDKN2A</i>) and 52 downregulated hub genes (such as <i>TP53, PCNA, BRCA1, CCNB1,</i> and <i>MSH2</i>) in MM that is targeted by DEmiRs. The expression of DEmiRs targeted two hub genes (<i>CDKN2A</i> and <i>TP53</i>) are correlated with the survival prognosis of MM patients. Furthermore, the expression level of <i>CDKN2A</i> is correlated with immune signatures, including CD4+ Regulatory T cells, T cell exhaustion, MHC Class I, immune checkpoint genes, macrophages, neutrophils, and TH2 cells in the TME of MM. Finally, we revealed the consistently deregulated expression level of key gene <i>CDKN2A</i> and its co-regulatory DEmiRs, including hsa-mir-192, hsa-mir-10b, hsa-mir-492, and hsa-mir-24 in the independent cohorts of MM. Identifying key genes and miRNA-mRNA regulatory networks may provide new molecular insights into the tumor immune microenvironment in MM.