Bhattacharya, Animesh, Schmitz, Ulf, Raatz, Yvonne, Schönherr, Madeleine, Kottek, Tina, Schauer, Marianne, Franz, Sandra, Saalbach, Anja, Anderegg, Ulf, Wolkenhauer, Olaf, Schadendorf, Dirk, Simon, Jan C., Magin, Thomas, Vera, Julio, and Kunz, Manfred (2015) miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy. Oncotarget, 6. pp. 2966-2980.

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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.

Item ID:	68996
Item Type:	Article (Research - C1)
ISSN:	1949-2553
Copyright Information:	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Date Deposited:	19 Dec 2024 01:44
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321101 Cancer cell biology @ 80% 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 20%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 40% 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280112 Expanding knowledge in the health sciences @ 60%
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