Intronic MiR-211 Assumes the Tumor Suppressive Function of Its Host Gene in Melanoma

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Nov 27

PMID 21109473

Citations 135

Authors

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

Affiliations

Soon will be listed here.

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.

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