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Transcription factor/microRNA axis blocks melanoma invasion program by miR-211 targeting NUAK1

Bell, RE and Khaled, M and Netanely, D and Schubert, S and Golan, T and Buxbaum, A and Janas, MM and Postolsky, B and Goldberg, MS and Shamir, R and Levy, C (2014) Transcription factor/microRNA axis blocks melanoma invasion program by miR-211 targeting NUAK1. Journal of Investigative Dermatology. pp. 441-451.

Abstract

Melanoma is one of the deadliest human cancers, responsible for approximately 80% of skin cancer mortalities. The aggressiveness of melanoma is due to its capacity to proliferate and rapidly invade surrounding tissues, leading to metastases. A recent model suggests melanoma progresses by reversibly switching between proliferation and invasion transcriptional signatures. Recent studies show that cancer cells are more sensitive to microRNA (miRNA) perturbation than are non-cancer cells; however, the roles of miRNAs in melanoma plasticity remain unexplored. Here, we use the gene expression profiles of melanoma and normal melanocytes to characterize the transcription factor-miRNA relationship that modulates the proliferative and invasive programs of melanoma. We identified two sets of miRNAs that likely regulate these programs. Interestingly, one of the miRNAs involved in melanoma invasion is miR-211, a known target of the master regulator microphthalmia-associated transcription factor (MITF). We demonstrate that miR-211 contributes to melanoma adhesion by directly targeting a gene, NUAK1. Inhibition of miR-211 increases NUAK1 expression and decreases melanoma adhesion, whereas upregulation of miR-211 restores adhesion through NUAK1 repression. This study defines the MITF/miR-211 axis that inhibits the invasive program by blocking adhesion. Furthermore, we have identified NUAK1 as a potential target for the treatment of metastatic melanoma. 2014 The Society for Investigative Dermatology

Item Type: Article
Additional Information: NIBR author: Janas, M institute: NIBR- address only contributor address: (Bell, Golan, Buxbaum, Postolsky, Levy) Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Khaled) Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, United States (Khaled, Schubert, Janas, Goldberg) Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States (Netanely, Shamir) Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel (Khaled) Institut Gustave Roussy, INSERM U753, Villejuif 94805, France (Schubert) Cenix BioScience GmbH, Dresden 01307, Germany (Janas) Novartis Institutes for BioMedical Research, Cambridge, MA 02139, United States
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22658

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