MiR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy (microRNA)
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ABSTRACT: MicroRNA (miRNA) expression profiling identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions compared with primary melanomas. miR-638 enhanced the tumourigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling of miR-638 and antagomir-transduced cells identified new candidate genes as miR-638 targets, the majority of which is involved in p53-mediated apoptosis regulation. miR-638 depletion stimulated expression of p53 and its downstream target genes and induced apoptosis and autophagy in melanoma cells. miR-638 promoter analysis revealed transcription factor associated protein 2-M-NM-1 (TFAP2A) as a direct negative regulator of miR-638. Further analyses provided strong evidence for a double negative regulatory feedback loop between miR-638 and TFAP2A. Taken together, miR-638 may support melanoma progression by suppressing p53-mediated apoptosis pathways and by targeting the transcriptional repressor TFAP2A. TaqManM-BM-. low-density arrays (TLDA; human microRNA Cards A v2.1 & B v2.0, Applied Biosystems, Darmstadt, Germany) were used for measuring the expression of 667 human miRNAs in primary melanomas (PM, n=8), lymph node metastases (LNM, n=9) or distant cutaneous metastases (DCM, n=10).
ORGANISM(S): Homo sapiens
SUBMITTER: Animesh Bhattacharya
PROVIDER: E-GEOD-54492 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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