title: Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor.
abstract: To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.
authors: Drug Discovery Group, Division of Cancer & Cell Biology, Queensland Institute of Medical Research, Brisbane, QLD, Australia. Glen.Boyle@qimr.edu.au  
authors: Glen M
authors: GM
authors: Boyle
authors: Susan L
authors: SL
authors: Woods
authors: Vanessa F
authors: VF
authors: Bonazzi
authors: Mitchell S
authors: MS
authors: Stark
authors: Elke
authors: E
authors: Hacker
authors: Lauren G
authors: LG
authors: Aoude
authors: Ken
authors: K
authors: Dutton-Regester
authors: Anthony L
authors: AL
authors: Cook
authors: Richard A
authors: RA
authors: Sturm
authors: Nicholas K
authors: NK
authors: Hayward
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018398:Homeodomain Proteins; C549405:MIRN211 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D050809:POU Domain Factors; D012334:RNA, Neoplasm; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; C085076:transcription factor Brn-2