A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in Breast Cancer

摘要: The transformation of a normal cell to cancer requires the derail multiple pathways. Normal signaling in is regulated at stages by presence feedback loops, calibration levels proteins their turnover, and posttranscriptional regulation, name few. tumor suppressor protein FBXO31 component SCF E3 ubiquitin ligase required arrest cells G1 following genotoxic stresses. Due its growth-suppression activity, it underexpressed many cancers. However, molecular mechanism underlying translational regulation remains unclear. Here we show that oncogenic microRNAs miR-93 miR-106a repress FBXO31, resulting upregulation Slug, which involved epithelial-mesenchymal transition invasion. targets ubiquitylates Slug for proteasomal degradation. this repressed breast tumors where are overexpressed. Our study further unravels an interesting whereby drives expression miR-106a, thus establishing positive loop maintain invasive phenotype. Together, these results establish interplay between ubiquitination machinery, together regulate