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

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.

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@inproceedings{Bhattacharya2015miR638PM, title={miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy}, author={Animesh Bhattacharya and Ulf Schmitz and Yvonne Raatz and Madeleine Sch{\"{o}nherr and Tina Kottek and Marianne Schauer and Sandra Franz and Anja Saalbach and Ulf Anderegg and Olaf Wolkenhauer and Dirk Schadendorf and Jan C. Simon and Thomas Michael Magin and Julio Vera and Manfred Kunz}, booktitle={Oncotarget}, year={2015} }