title: Induction of exportin-5 expression during melanoma development supports the cellular behavior of human malignant melanoma cells.
abstract: Regulation of gene expression via microRNAs is known to promote the development of many types of cancer. In melanoma, miRNAs are globally up-regulated, and alterations of miRNA-processing enzymes have already been identified. However, mis-regulation of miRNA transport has not been analyzed in melanoma yet. We hypothesized that alterations in miRNA transport disrupt miRNA processing. Therefore, we investigated whether the pre-miRNA transporter Exportin-5 (XPO5) was involved in altered miRNA maturation and functional consequences in melanoma. We found that XPO5 is significantly over-expressed in melanoma compared with melanocytes. We showed enhanced XPO5 mRNA stability in melanoma cell lines which likely contributes to up-regulated XPO5 protein expression. In addition, we identified MEK signaling as a regulator of XPO5 expression in melanoma. Knockdown of XPO5 expression in melanoma cells led to decreased mature miRNA levels and drastic functional changes. Our data revealed that aberrant XPO5 expression is important for the maturation of miRNAs and the malignant behavior of melanoma cells. We suggest that the high abundance of XPO5 in melanoma leads to enhanced survival, proliferation and metastasis and thereby supports the aggressiveness of melanoma.
authors.affiliation: Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Corinna Anna
authors.initials: CA
authors.lastname: Ott
authors.affiliation: Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Linck
authors.affiliation: Institute of Molecular Immunology, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), 81377 Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 093053 Regensburg, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
authors.affiliation: Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.|Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Anja Katrin
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D028884:Karyopherins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C446511:XPO5 protein, human
keywords: XPO5; mRNA stability; malignant melanoma; miR-SNP; microRNA