Oncotarget

Research Papers:

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

Corinna Anna Ott, Lisa Linck, Elisabeth Kremmer, Gunter Meister and Anja Katrin Bosserhoff _

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Oncotarget. 2016; 7:62292-62304. https://doi.org/10.18632/oncotarget.11410

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Abstract

Corinna Anna Ott1, Lisa Linck1, Elisabeth Kremmer3, Gunter Meister2, Anja Katrin Bosserhoff1,4

1Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany

2Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 093053 Regensburg, Germany

3Institute of Molecular Immunology, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), 81377 Munich, Germany

4Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany

Correspondence to:

Anja Katrin Bosserhoff, email: [email protected]

Keywords: malignant melanoma, microRNA, XPO5, miR-SNP, mRNA stability

Received: March 23, 2016    Accepted: August 09, 2016    Published: August 19, 2016

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.


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