ObjectivesThe etiology of multiple myeloma (MM) is unknown and it remains incurable. We sought to elucidate the mechanisms underlying miRNAs involvement in MM pathogenesis. MethodsPublic mRNA and miRNA expression datasets for MM were collected from the Gene Expression Omnibus database. By integrated bioinformatics analysis, the expression signatures were identified and the miRNA-mRNA interaction network was constructed. The potential functions of target genes were then explored by functional enrichment analysis. ResultsTotally, 839 differentially expressed mRNAs and six differentially expressed miRNAs were identified. The context of miRNAs-mediated genes regulatory network consisted of 288 possible miRNA-mRNA target pairs. The hub miRNA was hsa-miR-92a, which can serve as the indicator for MM disease status. Another miRNA, hsa-miR-148a, could be useful for prognosis of MM. Functional annotation revealed that the miRNA targets may play important roles in viral infection and proteasome. Moreover, miRNA targets may be involved in renal cell carcinoma and other nervous system disease such as Huntington's disease, Alzheimer's disease and Parkinson's disease, which may be subsequent complications of MM. ConclusionsInfections could be a leading cause for the morbidity of MM patients. The crucial protein degradation machinery may be essential in the pathogenesis of MM.