Bemis Lynne T, Chen Robert, Amato Carol M, Classen Elizabeth H, Robinson Steven E, Coffey David G, Erickson Paul F, Shellman Yiqun G, Robinson William A
Division of Medical Oncology, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
Cancer Res. 2008 Mar 1;68(5):1362-8. doi: 10.1158/0008-5472.CAN-07-2912.
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.
小眼畸形相关转录因子（MITF）是黑素细胞发育、存活及功能的主要调节因子。在黑色素瘤中检测到MITF表达频繁改变，但其表达改变的潜在机制尚未完全明确。在这些研究中，我们已确定微小RNA - 137（miR - 137）是MITF表达的调节因子。位于1号染色体1p22的miR - 137基因组位点使其处于人类基因组中先前确定为携带黑色素瘤易感性等位基因的区域。在此，我们表明黑色素瘤细胞系中成熟miR - 137的表达下调了MITF的表达。此外，我们在pre - miR - 137序列上游5'端鉴定出一个15个碱基的可变核苷酸串联重复序列，它改变了黑色素瘤细胞系中miR - 137的加工及功能。
