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Ott, C.A.* ; Linck, L.* ; Kremmer, E. ; Meister, G.* ; Bosserhoff, A.K.*

Induction of exportin-5 expression during melanoma development supports the cellular behavior of human malignant melanoma cells.

Oncotarget 7, 62292-62304 (2016)
Verlagsversion Anhang DOI PMC
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Xpo5 ; Mrna Stability ; Malignant Melanoma ; Mir-snp ; Microrna; Single-nucleotide Polymorphisms; Mediates Nuclear Export; Protein-kinase Kinase; Double-stranded-rna; Microprocessor Complex; Microrna Biogenesis; Argonaute Proteins; Cancer; Inhibitor; Gene
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 7, Heft: 38, Seiten: 62292-62304 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Verlagsort Albany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)