Identification of potential molecular players and therapeutic drug molecules in Melphalan resistant Multiple myeloma by integrated bioinformatics analysis

Abstract

Multiple myeloma (MM), second most common haematological malignancy, still remains incurable with the acquiring of drug resistance. Melphalan therapy which has been used as one of the key therapies against MM, is impeded by the occurrence of Melphalan resistance. The precise underlying mechanism of this acquired Melphalan resistance in MM is not yet well deciphered. Therefore, this present study was aimed to identify the differentially expressed genes (DEGs) associated micro RNAs (miRNAs) and transcription factors (TFs) from the microarray dataset of Melphalan resistant and Melphalan sensitive MM cell lines, obtained from Gene Expression Omnibus (GEO) database. DEGs were analysed using GEO2R tool from the dataset. Then the gene ontology (GO) and pathway enrichment analysis were executed by using DAVID database. Protein-protein interaction (PPI) network of DEGs was constructed and analysed by using STRING database and Cytoscape tool. Genetic alterations in DEGs were studied through COSMIC database. Network of interaction of DEGs and miRNAs as well as TFs was constructed and analysed by using mirDIP, TRRUST and miRNet tools. Drug gene interaction was examined to identify potential drug molecules by DGIdb tool. Various DEGs that might play pivotal role in Melphalan resistant MM, were detected and selected for further analysis. miRNA analysis detected hsa-mir- 21-3p, hsa-mir-27a-5p, hsa-mir-129-2-3p that could interact with maximum target DEGs. One TF, STAT1 was found to regulate the expression of selected DEGs. The whole study may give a better understanding about the Melphalan resistance in MM.