Sox4-mediated Dicer expression is critical for suppression of melanoma cell invasion
| Autor: | Seyed Mehdi Jafarnejad, Gang Li, Gholamreza Safaee Ardekani, Magdalena Martinka, Mazyar Ghaffari |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Ribonuclease III Cytoplasm Cancer Research Skin Neoplasms genetic processes Gene Expression Kaplan-Meier Estimate Biology Article SOXC Transcription Factors DEAD-box RNA Helicases 03 medical and health sciences SOX4 0302 clinical medicine Invasion Cell Line Tumor microRNA Gene expression Genetics medicine Humans Neoplasm Invasiveness Promoter Regions Genetic Melanoma Molecular Biology Transcription factor miRNA 030304 developmental biology Regulation of gene expression 0303 health sciences Gene knockdown fungi food and beverages Middle Aged medicine.disease 3. Good health Gene Expression Regulation Neoplastic MicroRNAs enzymes and coenzymes (carbohydrates) 030220 oncology & carcinogenesis Cancer research biology.protein Sox4 Female Dicer Protein Binding |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2012.239 |
| Popis: | We previously reported reduced expression of Sox4 in metastatic melanoma and its role in suppression of cell migration and invasion through inhibition of nuclear factor (NF)-κB p50. Sox4 can also bind to the promoter sequence of Dicer, a microRNA (miRNA) biogenesis factor. Interestingly, altered expression of Dicer was also observed in cancers. However, the potential mechanisms that regulate Dicer expression and its potential significance in melanoma progression are unknown. Here, we studied the regulation of Dicer expression by Sox4 and its role in suppression of melanoma invasion. Our data showed that Sox4 positively regulates Dicer expression by binding to its promoter sequences and enhancing its activity. We found that knockdown of Dicer enhances the matrigel invasion of melanoma cells by at least twofold. In addition, we revealed that overexpression of exogenous Dicer reverts the enhanced melanoma cell invasion upon Sox4 knockdown. Furthermore, we examined the expression of Dicer protein in a large set of melanocytic lesions (n=514) at different stages by tissue microarray and found that Dicer expression is inversely correlated with melanoma progression (P |
| Databáze: | OpenAIRE |
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