Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer
Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer
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DOI：
10.1002/ijc.25919
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Lin, Wen-Chang
中科院分区：
文献类型：
--
作者：
Tsai, Kuo-Wang;Wu, Chew-Wun;Lin, Wen-Chang
MicroRNAs(MiRNAs)是一种小的非编码RNA，通过靶向特定基因的表达而在不同的生物和病理过程中发挥基础作用。在这38个miRNAs中，我们进一步分析了miR-34b、miR-127-3p、miR-129-3p和miR-409，因为预测它们附近有CpG岛。这些miRNAs甲基化沉默的表达可以通过去甲基化药物以时间依赖的方式在胃癌细胞中重新激活。对这些miRNAs甲基化状态的分析表明，与癌旁正常组织相比，mir-34b和mir-129-2的上游CpG富集区在胃癌组织中频繁发生甲基化，并且其甲基化状态与其表达模式呈负相关。MiR-34b和miR-129-3p在胃癌组织中的表达受DNA高甲基化的影响，其低表达与胃癌的临床病理特征有关。综上所述，我们的研究表明，肿瘤特异性甲基化沉默了胃癌细胞中的miR-34b和miR-129。
MicroRNAs (miRNAs) are small noncoding RNAs that play fundamental roles in diverse biological and pathological processes by targeting the expression of specific genes. Here, we identified 38 methylation-associated miRNAs, the expression of which could be epigenetically restored by cotreatment with 5-aza-20-deoxycytidine and trichostatin A. Among these 38 miRNAs, we further analyzed miR-34b, miR-127-3p, miR-129-3p and miR-409 because CpG islands are predicted adjacent to them. The methylation-silenced expression of these miRNAs could be reactivated in gastric cancer cells by treatment with demethylating drugs in a time-dependent manner. Analysis of the methylation status of these miRNAs showed that the upstream CpG-rich regions of mir-34b and mir-129-2 are frequently methylated in gastric cancer tissues compared to adjacent normal tissues, and their methylation status correlated inversely with their expression patterns. The expression of miR-34b and miR-129-3p was downregulated by DNA hypermethylation in primary gastric cancers, and the low expression was associated with poor clinicopathological features. In summary, our study shows that tumor-specific methylation silences miR-34b and miR-129 in gastric cancer cells.