Suppressor microRNA-145 Is Epigenetically Regulated by Promoter Hypermethylation in Esophageal Squamous Cell Carcinoma.
Suppressor microRNA-145 Is Epigenetically Regulated by Promoter Hypermethylation in Esophageal Squamous Cell Carcinoma.
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发表时间：
2015-09
影响因子：
2
通讯作者：
K. Harada;Y. Baba;T. Ishimoto;K. Kosumi;R. Tokunaga;Daisuke Izumi;M. Ohuchi;Kenichi Nakamura;
中科院分区：
文献类型：
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作者：
K. Harada;Y. Baba;T. Ishimoto;K. Kosumi;R. Tokunaga;Daisuke Izumi;M. Ohuchi;Kenichi Nakamura;
背景/目的 DNA 甲基化是癌症中常见的表观遗传变化。然而，食管鳞状细胞癌 (ESCC) 中表观遗传改变（尤其是 CpG 岛高甲基化）对 microRNA (miRNA) 的调节仍知之甚少。材料和方法 使用 Human miFinder 384HC miScript miRNA PCR 阵列分析用 5-aza-2'-脱氧胞苷 (5-AZA) 去甲基化后上调的 miRNA。通过亚硫酸氢盐-焦磷酸测序测定评估DNA甲基化水平。结果 在两个细胞系中，发现 20 个 miRNA（包括 miR-145-5p）在 5-AZA 处理后上调超过三倍。与匹配的正常相邻食管上皮粘膜相比，癌组织中的 miRNA-145 启动子显着更高甲基化（p=0.0042；配对 t 检验）。此外，癌组织中的 miRNA-145-5p 表达水平显着降低（p=0.0024）。结论 ESCC 中 miRNA-145 的表达似乎受到 miRNA-145 启动子区域高甲基化的调节。
BACKGROUND/AIM DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS miRNAs which were up-regulated after de-methylation with 5-aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay. RESULTS In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145-5p expression levels were significantly lower in cancerous tissues (p=0.0024). CONCLUSION miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.