Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor
Miguel F Segura, Douglas Hanniford, Silvia Menendez, Linsey Reavie, Xuanyi Zou, Silvia Alvarez-Diaz, Jan Zakrzewski, Elen Blochin, Amy Rose, Dusan Bogunovic, David Polsky, Jianjun Wei, Peng Lee, Ilana Belitskaya-Levy, Nina Bhardwaj, Iman Osman, Eva Hernando
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2009
The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly up-regulated in human melanoma cell lines and tissue samples; this up-regulation correlates with gene copy number in a subset of melanoma cell lines. Moreover, miR-182 ectopic expression stimulates migration of melanoma cells in vitro and their metastatic potential in vivo, whereas miR-182 down-regulation impedes invasion and triggers apoptosis. We further show that miR-182 ove..View full abstract
Awarded by NYU Cancer Center (National Institutes of Health-National Cancer Institute Cancer Center)
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES
We thank Dr. Jiri Zavadil and members of the New York University Cancer Institute Genomics Facility for array profiling, as well as the services of theNYUExperimental Pathology Core Facilities. Weare grateful to Dr. Dorothy Bennett (University College London) for providing us with Hermes cells, Dr. AlanHoughton(MemorialSloan-Kettering Cancer Center) for the SK-MEL cell lines, and to Dr. Meenhard Herlyn (Wistar Institute) for the primary melanoma cell lines. This work was funded by grants of the NYU Cancer Center (National Institutes of Health-National Cancer Institute Cancer Center Support Grant P30CA016087) and the Elsa U. Pardee Foundation. M. F. S. is supported by an Alfonso Martin-Escudero fellowship.