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 Pinner, 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

Research output: Contribution to journalArticlepeer-review

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
StatePublished - 10 Dec 2010
Externally publishedYes

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