MicroRNA-137 Targets Microphthalmia-Associated Transcription Factor in Melanoma Cell Lines

Abstract

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. [Cancer Res 2008;68(5):1362-8]

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

“…37 Another miRNA, miRNA-137, was reported to reduce MITF-M expression in melanoma cell lines. 38 We could not document an induction of miRNA-137 by IL-1b (data not shown). We report here that the level of expression of the IL-1 receptor (IL1R1) is an important parameter to determine the ability of melanoma cells to respond to IL-1.…”

miR-193b Regulates Mcl-1 in Melanoma

“…10 For example, miR-137 targets microphthalmia-associated transcription factor, which is the master regulator of melanocyte development, survival, and function. 11 The miR-221/222 oncogenes promote proliferation and dedifferentiation of melanoma cells by repressing c-Kit and p27Kip. 12 miR-182 enhances melanoma metastasis by targeting FOXO3 and microphthalmia-associated transcription factor.…”

MicroRNA-218 inhibits melanogenesis by directly suppressing microphthalmia-associated transcription factor expression

“…Six of these have been reported to suppress MITF expression, and miR-27a is reported to have no interaction with MITF 3'-UTR. [7][8][9][10][11][12][13][14] Only miR-218 shows an association with MITF and melanogenesis, as shown for the first time in this study.…”

“…According to the prediction, miR-218 was an excellent one among the eight candidates and the interaction between miR-218 and Mitf 3'-UTR is a novel hypothesis. [7][8][9][10][11][12][13][14] In addition, the forskolin-and UV radiation-mediated downregulation of miR-218 has been observed in melan-a cells, suggesting that miR-218 has a regulatory role in the MITF-mediated melanogenic process. …”