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Mol Cell. 2010 Dec 10;40(5):841-9. doi: 10.1016/j.molcel.2010.11.020. Epub 2010 Nov 25.

Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma.

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  • 1Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID:
21109473
[PubMed - indexed for MEDLINE]
PMCID:
PMC3004467
Free PMC Article
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