Oncogenic B-Raf signaling in melanoma cells controls a network of microRNAs with combinatorial functions
| Autor: | Natalie G. Ahn, M M Gross, Emily M. Anderson, Kasey L. Couts, K A Sullivan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Proto-Oncogene Proteins B-raf
MAPK/ERK pathway Cancer Research U0126 MAP Kinase Signaling System MAP Kinase Kinase 2 MAP Kinase Kinase 1 Biology 03 medical and health sciences 0302 clinical medicine RNA interference microRNA melanoma Tumor Cells Cultured Genetics medicine Humans Neoplasm Invasiveness RNA Small Interfering Molecular Biology Cell Proliferation Oligonucleotide Array Sequence Analysis 030304 developmental biology Regulation of gene expression 0303 health sciences Cell growth Melanoma B-Raf Cancer medicine.disease microRNAs Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Mutation Cancer cell Cancer research Melanocytes Original Article RNA Interference microarray |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2012.209 |
| Popis: | Over two-thirds of melanomas have activating mutations in B-Raf, leading to constitutive activation of the B-Raf/MKK/ERK signaling pathway. The most prevalent mutation, B-RafV600E, promotes cancer cell behavior through mechanisms that are still incompletely defined. Here, we used a sensitive microarray profiling platform to compare microRNA (miRNA) expression levels between primary melanocytes and B-RafV600E-positive melanoma cell lines, and between melanoma cells treated in the presence and absence of an MKK1/2 inhibitor. We identified a network of >20 miRNAs deregulated by B-Raf/MKK/ERK in melanoma cells, the majority of which modulate the 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. We show that miRNAs augment effects on protein repression and cell invasion when co-expressed, and gene-specific latency and interference effects between miRNAs were also observed. 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 network. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|