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

Carmit Levy, Mehdi Khaled, Dimitrios Iliopoulos, Maja M Janas, Steffen Schubert, Sophie E Acton, Po-Hao Chen, Shuqiang Li, Anne L Fletcher, Satoru Yokoyama, Kenneth L Scott, Levi A Garraway, Jun S Song, Scott R Granter, Shannon J Turley, David E Fisher, Carl D Novina

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204 Citations (Scopus)

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 languageEnglish
Pages (from-to)841 - 849
Number of pages9
JournalMolecular Cell
Volume40
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

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