Micro-RNA (miRNA) expression and function have been shown to be highly dependent upon the experimental system considered. Here we present a systems view of miRNA expression analysis in-vivo that may assist in identification of effective novel therapeutic approaches. Specifically, we show how combined information regarding expression of mature micro-RNAs (miRNA) and of the miRNA host-gene (upstream) and miRNA targets (downstream) can be integrated into analysis of clinical samples, to both discover and assess prognostic miRNAs and their associated pathways, and to discover novel miRNA targets.