Abstract
When it escapes early detection, malignant melanoma becomes a highly lethal and treatment-refractory cancer. Melastatin is greatly downregulated in metastatic melanomas and is widely believed to function as a melanoma tumor suppressor. Here we report that tumor suppressive activity is not mediated by melastatin but instead by a microRNA (miR-211) hosted within an intron of melastatin. Increasing expression of miR-211 but not melastatin reduced migration and invasion of malignant and highly invasive human melanomas characterized by low levels of melastatin and miR-211. An unbiased network analysis of melanoma-expressed genes filtered for their roles in metastasis identified three central node genes: IGF2R, TGFBR2, and NFAT5. Expression of these genes was reduced by miR-211, and knockdown of each gene phenocopied the effects of increased miR-211 on melanoma invasiveness. These data implicate miR-211 as a suppressor of melanoma invasion whose expression is silenced or selected against via suppression of the entire melastatin locus during human melanoma progression.
Original language | English |
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Pages (from-to) | 841-9 |
Number of pages | 9 |
Journal | Molecular Cell |
Volume | 40 |
Issue number | 5 |
DOIs | |
Publication status | Published - 10 Dec 2010 |
Bibliographical note
Copyright © 2010 Elsevier Inc. All rights reserved.Keywords
- Cell Line, Tumor
- Down-Regulation
- Gene Expression Regulation, Neoplastic
- Genes, Tumor Suppressor
- Humans
- Introns
- Melanoma
- MicroRNAs
- NFATC Transcription Factors
- Protein-Serine-Threonine Kinases
- Receptors, Transforming Growth Factor beta
- Skin Neoplasms