title: miR-20b regulates expression of proteinase-activated receptor-1 (PAR-1) thrombin receptor in melanoma cells.
abstract: The proteinase-activated receptor 1 (PAR-1) plays a central role in melanoma progression and its expression level is believed to correlate with the degree of cancer invasiveness. Here, we show that PAR-1 is post-transcriptionally regulated by miR-20b microRNA in human melanoma cells. PAR-1 was found to be expressed in metastatic melanoma cells but was barely detectable in primary melanoma. By transducing primary melanoma cells with a lentivirus containing a 3'-UTR construct of PAR-1 mRNA, we could show that endogenous melanoma microRNAs interacted with PAR-1 3'-UTR and silenced a fused luciferase reporter. Transfection of an inhibitor against miR-20b into primary melanoma cells reversed this process. Finally, transfection of miR-20b mimic into metastatic melanoma cells caused downregulation of the luciferase reporter. We conclude that miR-20b regulates expression of melanoma PAR-1 receptor, which may explain the differential expression of PAR-1 observed in human melanoma.
authors.affiliation: Division of Microbiology and Molecular Medicine, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Amina
authors.initials: A
authors.lastname: Saleiban
authors.forename: Lars
authors.initials: L
authors.lastname: Faxälv
authors.forename: Kjersti
authors.initials: K
authors.lastname: Claesson
authors.forename: Jan-Ingvar
authors.initials: JI
authors.lastname: Jönsson
authors.forename: Abdimajid
authors.initials: A
authors.lastname: Osman
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D017930:Genes, Reporter; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D044463:Receptor, PAR-1 / Q000096:biosynthesis* / Q000235:genetics; D013917:Thrombin / Q000096:biosynthesis
chemical_list: D020413:3' Untranslated Regions; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D044463:Receptor, PAR-1; D013917:Thrombin
keywords: gene expression regulation; melanoma; metastasis; microRNAs; proteinase-activated receptor-1