miR-146a promotes the initiation and progression of melanoma by activating Notch signaling

• DOI: 10.7554/elife.01460
• Publication Date: 2014-02-18T16:28:26Z
• Authors: Matteo Forloni; Shaillay Kumar Dogra; Yuying Dong; Darryl Conte; Jianhong Ou; Lihua Julie Zhu; April Deng; Meera Mahalingam; Michael R Green; Narendra Wajapeyee
• Keywords: Hes3 signaling axis

Oncogenic mutations in BRAF and NRAS occur 70% of melanomas. In this study, we identify a microRNA, miR-146a, that is highly upregulated by oncogenic NRAS. Expression miR-146a increases the ability human melanoma cells to proliferate culture form tumors mice, whereas knockdown has opposite effects. We show these activities are due targeting NUMB mRNA, repressor Notch signaling. Previous studies have shown pre-miR-146a contains single nucleotide polymorphism (C>G rs2910164). find pre-miR-146a/G activate signaling promote oncogenesis substantially higher than pre-miR-146a/C. Analysis cell lines matched patient samples indicates during progression enriched relative pre-miR-146a/C, resulting from C-to-G somatic mutation Collectively, our results reveal central role for initiation melanoma.