Retrotransposon Hypomethylation in Melanoma and Expression of a Placenta-Specific Gene

In the human placenta, DNA hypomethylation permits the expression of retrotransposon-derived genes that are normally silenced by methylation in somatic tissues. We previously identified hypomethylation of a retrotransposon-derived transcript of the voltage-gated potassium channel gene KCNH5 that is expressed only in human placenta. However, an RNA sequence from this placental-specific transcript has been reported in melanoma. This study examined the promoter methylation and expression of the retrotransposon-derived KCNH5 transcript in 25 melanoma cell lines to determine whether the acquisition of ‘placental’ epigenetic marks is a feature of melanoma. Methylation and gene expression analysis revealed hypomethylation of this retrotransposon in melanoma cell lines, particularly in those samples that express the placental KCNH5 transcript. Therefore we propose that hypomethylation of the placental-specific KCNH5 promoter is frequently associated with KCNH5 expression in melanoma cells. Our findings show that melanoma can develop hypomethylation of a retrotransposon-derived gene; a characteristic notably shared with the normal placenta.在人类胎盘中，DNA低甲基化（DNA hypomethylation）可使通常在体细胞组织中被甲基化沉默的逆转录转座子衍生基因（retrotransposon-derived genes）得以表达。我们此前曾鉴定出一种仅在人类胎盘中表达的、源自电压门控钾通道基因KCNH5的逆转录转座子转录本的低甲基化状态。然而，有报道称在黑色素瘤（melanoma）中存在该胎盘特异性转录本的RNA序列（RNA sequence）。本研究针对25株黑色素瘤细胞系中该逆转录转座子衍生的KCNH5转录本的启动子甲基化（promoter methylation）与表达情况展开分析，以探究"胎盘样"表观遗传标记（epigenetic marks）的获得是否为黑色素瘤的特征之一。甲基化与基因表达分析结果显示，黑色素瘤细胞系中该逆转录转座子存在低甲基化现象，尤其在表达胎盘型KCNH5转录本的样本中更为显著。据此，我们提出：胎盘特异性KCNH5启动子的低甲基化常与黑色素瘤细胞中KCNH5的表达相关。本研究结果表明，黑色素瘤可出现逆转录转座子衍生基因的低甲基化，而该特征与正常胎盘显著共有。