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.
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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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