miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy
Journal Publication ResearchOnline@JCUAbstract
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.
Journal
Oncotarget
Publication Name
N/A
Volume
6
ISBN/ISSN
1949-2553
Edition
N/A
Issue
N/A
Pages Count
15
Location
N/A
Publisher
Impact Journals
Publisher Url
N/A
Publisher Location
N/A
Publish Date
N/A
Url
N/A
Date
N/A
EISSN
N/A
DOI
10.18632/oncotarget.3070