Abstract 5245: A network of microRNAs contolled by oncogenic B-Raf signaling in melanoma cells

Abstract

Constitutive activation of the B-Raf/MKK/ERK signaling pathway a result of B-Raf activating mutations is a hallmark of over two-thirds of melanomas. The most prevalent mutation, B-RafV600E, promotes cancer cell behavior through mechanisms which are still incompletely defined. We utilized microRNA (miRNA) microarray profiling to identify a network of more than 20 miRNAs deregulated by B-Raf/MKK/ERK in melanoma cells, the majority of which modulate expression of key cancer regulatory genes and functions. Importantly, miRNAs within the network converge on protein regulation and cancer phenotypes, suggesting that these miRNAs might function combinatorially. Additionally, by altering functional levels of these miRNAs in cells with miRNA mimics and inhibitors we demonstrate that miRNAs augment effects on protein repression and cell invasion when co-expressed, and we also observe gene-specific latency and interference effects between miRNAs. Thus, B-Raf/MKK/ERK controls key aspects of cancer cell behavior and gene expression by modulating a network of miRNAs with cross-regulatory functions. The findings highlight the potential for complex interactions between coordinately regulated miRNAs within a gene expression network. Citation Format: Kasey L. Couts, Emily M. Anderson, Maren M. Gross, Kevin Sullivan, Natalie G. Ahn. A network of microRNAs contolled by oncogenic B-Raf signaling in melanoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5245. doi:10.1158/1538-7445.AM2014-5245