Global miRNA regulation of the EGFR-driven cell-cycle protein network
18/09/2012 - Room C209/10 at 14:00 - External Seminar
The EGFR-driven cell-cycle pathway has been extensively studied also because of its role in cancer. While several studies reported regulation of individual pathway components by microRNAs (miRNAs), we were out to study how miRNAs modulate the EGFR protein network at a global level. A large-scale miRNA screening approach was combined with a quantitative proteomic readout to uncover potential regulatory modules. Network-analysis revealed miRNAs simultaneously co-regulating several proteins that act in the same functional module. There, miR-124, miR-147 and miR-193a-3p co-target EGFR-driven cell-cycle network proteins and inhibit cell-cycle progression and proliferation in our breast cancer model system. The redundancy in the activities of individual miRNAs as well as in their regulation of target mRNAs indicates the high complexity of the regulatory network by miRNAs that may have implications for the potential of miRNAs for use as therapeutic molecules.