Fig. 1

Analysis pipeline. Differentially expressed gene lists in MPM from four public datasets (P < 0.05) were subjected to GSEA analysis using the C3 list in the Molecular Signatures Database (MSigDB v4.0) to identify enriched 3’UTR microRNA binding motifs [4]. The top 20 enriched microRNA motifs identified at P < 0.05 (False discovery rate adjusted) were considered significant and ranked between these four studies. Predicted target mRNAs from these enriched microRNA families were analyzed further using Gene Ontology (DAVID [68]) and Pathway Enrichment (Partek Genome Suite) to elucidate affected regulatory pathways. Confirmation of dysregulated candidate microRNA families in MPM cell lines (n = 7) and patient tumors (n = 59) were carried out using RT-qPCR. Furthermore, correlation of enriched microRNAs (downregulated) to gene expression of predicted targets (upregulated) were extracted based on our previous published array dataset [19]. Thus this analysis pipeline identifies and ranks candidate targets according to significance P value, correlation between miRNA-mRNA array data as well as being able to be targeted functionally by small molecule inhibitors