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

Levy, C; Khaled, M; Iliopoulos, D; Janas, MM; Schubert, S; Pinner, S; Chen, P-H; ... Novina, CD; + view all (2010) Intronic miR-211 Assumes the Tumor Suppressive Function of Its Host Gene in Melanoma. Molecular Cell , 40 (5) pp. 841-849. 10.1016/j.molcel.2010.11.020. Green open access

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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.

Type: Article
Title: Intronic miR-211 Assumes the Tumor Suppressive Function of Its Host Gene in Melanoma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.molcel.2010.11.020
Publisher version: https://doi.org/10.1016/j.molcel.2010.11.020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1387314
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