Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 430, Issue 2, Pages 706-710Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.11.086
Keywords
microRNA; Melanoma; Migration; Invasion; Metastasis; Signaling
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Funding
- National Health and Medical Research Council
- Cancer Council of Western Australia
- Medical Research Commercialization Fund of Australia
- Scott Kirkbride Melanoma Research Centre
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Aberrant expression of microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been implicated in the development and progression of melanoma. However, the precise mechanistic role of many of these miRNAs remains unclear. We have investigated the functional role of miR-7-5p in melanoma, and demonstrate that miR-7-5p expression is reduced in metastatic melanoma-derived cell lines compared with primary melanoma cells, and that when ectopically expressed miR-7-5p significantly inhibits melanoma cell migration and invasion. Additionally, we report that insulin receptor substrate-2 (IRS-2) is a target of miR-7-5p in melanoma cells, and using RNA interference (RNAi) we provide evidence that IRS-2 activates protein kinase B (Akt), and promotes melanoma cell migration. Thus, miR-7-5p may represent a novel tumor suppressor miRNA in melanoma, acting at least in part via its inhibition of IRS-2 expression and oncogenic Akt signaling. (C) 2012 Elsevier Inc. All rights reserved.
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