Identification of cell signaling pathway associated miRNAs in cancer cells using a systems biological approach: potent RNAi response in cancer using novel 2’-OMe-phosphorodithioated modified siRNAs

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules and on average only 22 nucleotides long that regulate gene expression at the post-transcriptional level. Target predictions of miRNA based on sequence are limited due to too many candidates resulting in high false positives. We generated the Association score matrix and miRNA-pathway association map. To validate our approach, we used miR-500 as an example to investigate the hypothetical target regulation mechanisms. We confirmed in-vitro that mir-500 highly is associated with ERK signaling pathway in breast cancer cells. Furthermore, we found PPFIA1 might be one of direct targets of miR-500 to regulate activating the ERK pathway. In conclusion, we developed a model system to systematically predict potential miRNA functional targets which play critical roles in cell signaling pathways from the NCI-60 genomic and proteomic data at whole genomic scale. Two groups of samples are included: 1. siControl treated control-miRNA and 2. mimic miR-500 treated two cells: MCF7 and MDA-MB-231. Gene expression profiles of mimic miR-500 treated cells were compared to that of control treated cells.