期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 379, 期 3, 页码 790-794出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.12.152
关键词
cKit; MicroRNA; Cutaneous melanoma; Melanocytes; mir-221
资金
- Jefferson Medical College
Loss of ckit receptor in Cutaneous melanomas was attributed to the down-regulation of AP2 transcription factor. Our analysis of 27 melanoma cell lines showed no correlation between AP2 and c-kit expression. Suggesting a post-transcriptional mechanism of cKit clown-modulation, we performed genome-wide microRNA (miRNA) expression profiling and found that several miRNA species are commonly up-regulated in melanomas. Among them was mir-221, which can directly interact with c-kit 3'UTR and inhibit cKit protein translation. Observed inverse correlation of the c-kit and mir-221 expression in various melanocytic cells pointed to its involvement in regulation of cKit in melanoma. Moreover, a series of functional assays demonstrated that mir-221 could directly inhibit cKit, p27(Kip1) and, possibly, other pivotal proteins in melanoma. Collectively, the studies presented here indicate that mir-221 Could be a novel therapeutic target for the treatment of cutaneous melanoma. They also suggest that regulation of expression and functional activity of identified up-regulated miRNAs should be further studied in the context of malignant melanoma. (c) 2009 Elsevier Inc. All rights reserved.
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