Silencing of interferon regulatory factor gene 6 in melanoma.
Silencing of interferon regulatory factor gene 6 in melanoma.
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DOI：
10.1371/journal.pone.0184444
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Nakagawa H
中科院分区：
文献类型：
--
作者：
Nobeyama Y;Nakagawa H
位于基因 5' 区域的 CpG 岛（CGI；密集的 CpG 簇）的甲基化会抑制该基因的转录。干扰素调节因子6（IRF6）与干扰素的表达相关，干扰素被用作黑色素瘤的有效辅助治疗，并被视为肿瘤抑制因子。然而，人们对黑色素瘤中 IRF6 基因的甲基化状态知之甚少。目的是确定黑色素瘤中位于 IRF6 5' 区域的 CGI (5' IRF6 CGI) 的甲基化状态。进行定量实时甲基化特异性 PCR (RT-MSP) 和亚硫酸氢盐测序来检查 IRF6 基因甲基化状态。进行定量实时逆转录PCR（RT-PCR）来检查IRF6表达。在八个检查的黑色素瘤细胞系中，5' IRF6 CGI 的甲基化水平与细胞对干扰素-β 的敏感性完全呈负相关。这些甲基化水平在 IRF6 表达抑制的黑色素瘤细胞系中较高，而在 IRF6 表达的细胞系中较低。在 21 个临床黑色素瘤样本中，5'IRF6 CGI 的甲基化水平范围广泛，从 0.0% 到 65.4%，但在 24 个临床黑素细胞痣样本中，显示出 0.0% 到 7.2% 之间的狭窄低水平范围。除黑色素瘤亚型外，这些甲基化水平与临床参数无关。在黑色素瘤中，IRF6 因 5' IRF6 CGI 的 DNA 甲基化而异常沉默。 IRF6 的甲基化状态可能与黑色素瘤对干扰素的敏感性相关。
Methylation of a CpG island (CGI; a dense cluster of CpGs) located in the 5' region of a gene suppresses transcription of that gene. Interferon regulatory factor 6 (IRF6) is associated with the expression of interferon, which is used as an effective adjuvant therapy for melanoma, and is regarded as a tumor suppressor. However, little is known about the methylation status of the IRF6 gene in melanoma. The purpose was to determine the methylation status of the CGI located in the 5' region of IRF6 (5' IRF6 CGI) in melanoma. Quantitative real-time methylation-specific PCR (RT-MSP) and bisulfite sequencing were performed to examine IRF6 gene methylation status. Quantitative real-time reverse transcription-PCR (RT-PCR) was performed to examine IRF6 expression. The methylation level of the 5' IRF6 CGI was completely inversely correlated with cell sensitivity to interferon-β in eight examined melanoma cell lines. These methylation levels were high in the melanoma cell lines with suppression of IRF6 expression and were low in the cell lines with IRF6 expression. The methylation levels of the 5' IRF6 CGI ranged widely from 0.0% to 65.4% in 21 clinical melanoma samples but showed a narrow range of low levels between 0.0% to 7.2% in 24 clinical melanocytic nevus samples. These methylation levels were not associated with clinical parameters except for melanoma subtypes. IRF6 is aberrantly silenced by DNA methylation of the 5' IRF6 CGI in melanoma. The methylation status of IRF6 is potentially associated with the sensitivity of melanoma to interferon.
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影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
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特异性干扰素基因的不足与黑色素瘤的预后不良有关。
影响因子：
3.7
作者：
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作者：
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通讯作者：
TANIGUCHI, T