title: miRNA-7-5p inhibits melanoma cell migration and invasion.
abstract: 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.
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000, Australia.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Giles
authors.forename: Rikki A M
authors.initials: RA
authors.lastname: Brown
authors.forename: Michael R
authors.initials: MR
authors.lastname: Epis
authors.forename: Felicity C
authors.initials: FC
authors.lastname: Kalinowski
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leedman
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C526297:IRS2 protein, human; C549242:MIRN7-1 microRNA, human