MicroRNA-137 targets microphthalmia-associated transcription factor in melanoma cell lines
MicroRNA-137 targets microphthalmia-associated transcription factor in melanoma cell lines
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DOI：
10.1158/0008-5472.can-07-2912
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发表时间：
2008-03-01
期刊：
影响因子：
11.2
通讯作者：
Robinson, William A.
中科院分区：
文献类型：
--
作者：
Bemis, Lynne T.;Chen, Robert;Robinson, William A.
小眼症相关转录因子（MITF）是黑素细胞发育、存活和功能的主要调节因子。在黑色素瘤中检测到MITF表达的频繁改变，但表达改变的潜在机制尚未完全确定。在这些研究中，我们已经确定microRNA-137（miR-137）作为MITF表达的调节因子。位于染色体1 p22的miR-137基因组位点将其置于先前确定的人类基因组区域中，该区域具有黑色素瘤易感性的等位基因。在这里，我们发现成熟的miR-137在黑色素瘤细胞系中的表达下调了MITF的表达。此外，我们已经确定了一个15 bp的可变核苷酸串联重复序列，位于前体miR-137序列的5'端，它改变了黑色素瘤细胞系中miR-137的加工和功能。
Micropthalmia-associated transcription factor (MITF) is the master regulator of melanocyte development, survival, and function. Frequent alteration in the expression of MITF is detected in melanoma, but the mechanism(s) underlying the alteration in expression have not been completely determined. In these studies, we have identified microRNA-137 (miR-137) as a regulator of MITF expression. The genomic locus of miR-137 at chromosome 1p22 places it in a region of the human genome previously determined to harbor an allele for melanoma susceptibility. Here, we show that expression of mature miR-137 in melanoma cell lines down-regulates MITF expression. Further, we have identified a 15-bp variable nucleotide tandem repeat located just 5' to the pre-miR-137 sequence, which alters the processing and function of miR-137 in melanoma cell lines.