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Global microRNA level regulation of EGFR-driven cell-cycle protein network in breast cancer

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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 targeted proteomics readout to uncover potential regulatory modules. Network-analysis revealed miRNAs simultaneously co-regulating several proteins that act in the same functional modules. 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. Future work will embark on the tools generated during this screen and investigate the impact of the tested miRNAs on other, metastasis-relevant pathways. This shall help to generate a comprehensive map of the miRNA/pathway interaction network, and form the basis for experimental testing of combinatorial perturbations in the network aimed at abrogating cancer phenotypes.

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

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