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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)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal OncoTarget

Quellenangaben Volume: 7, Issue: 38, Pages: 62292-62304

Publisher Impact Journals LLC

Publishing Place Albany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Immunology (IMI)