title: 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.
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Animesh
authors: A
authors: Bhattacharya
authors: Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.
authors: Ulf
authors: U
authors: Schmitz
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Yvonne
authors: Y
authors: Raatz
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Madeleine
authors: M
authors: Schönherr
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Tina
authors: T
authors: Kottek
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Marianne
authors: M
authors: Schauer
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Sandra
authors: S
authors: Franz
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Anja
authors: A
authors: Saalbach
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Ulf
authors: U
authors: Anderegg
authors: Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.
authors: Olaf
authors: O
authors: Wolkenhauer
authors: Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
authors: Dirk
authors: D
authors: Schadendorf
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Jan C
authors: JC
authors: Simon
authors: Institute of Biology and Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
authors: Thomas
authors: T
authors: Magin
authors: Laboratory of Systems Tumor Immunology, Department of Dermatology, Faculty of Medicine, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Julio
authors: J
authors: Vera
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Manfred
authors: M
authors: Kunz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C572154:MIRN638 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C493673:TFAP2A protein, human; C495901:TP53 protein, human; C501283:TP53INP2 protein, human; D050656:Transcription Factor AP-2; D016159:Tumor Suppressor Protein p53
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