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Oncotarget. 2015 Feb 20;6(5):2966-80.

miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy.

Author information

1
Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
2
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.
3
Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
4
Institute of Biology and Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
5
Laboratory of Systems Tumor Immunology, Department of Dermatology, Faculty of Medicine, University of Erlangen-Nuremberg, Erlangen, Germany.

Abstract

The present study identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions of melanomas compared with primary melanomas. miR-638 enhanced the tumorigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling identified new candidate genes including TP53INP2 as miR-638 targets, the majority of which are involved in p53 signalling. Overexpression of TP53INP2 severely attenuated proliferative and invasive capacity of melanoma cells which was reversed by miR-638. Depletion of miR-638 stimulated expression of p53 and p53 downstream target genes and induced apoptosis and autophagy. miR-638 promoter analysis identified the miR-638 target transcription factor associated protein 2α (TFAP2A/AP-2α) as a direct negative regulator of miR-638, suggestive for a double-negative regulatory feedback loop. Taken together, miR-638 supports melanoma progression and suppresses p53-mediated apoptosis pathways, autophagy and expression of the transcriptional repressor TFAP2A/AP-2α.

PMID:
25650662
PMCID:
PMC4413631
DOI:
10.18632/oncotarget.3070
[Indexed for MEDLINE]
Free PMC Article

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