Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
Int J Cancer. 2011 Dec 1;129(11):2600-10. doi: 10.1002/ijc.25919.
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-2'-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.
微小 RNA（miRNAs）是小的非编码 RNA，通过靶向特定基因的表达，在多种生物和病理过程中发挥基本作用。在这里，我们鉴定了 38 个与甲基化相关的 miRNA，它们的表达可以通过 5-氮杂-2′-脱氧胞苷和曲古抑菌素 A 的共同处理来进行表观遗传恢复。在这 38 个 miRNA 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 miRNA 的甲基化沉默表达可以通过在时间依赖性方式用去甲基化药物处理在胃癌细胞中重新激活。这些 miRNA 的甲基化状态分析表明，与相邻正常组织相比，胃癌组织中 mir-34b 和 mir-129-2 的上游富含 CpG 的区域经常发生甲基化，并且它们的甲基化状态与它们的表达模式呈负相关。miR-34b 和 miR-129-3p 的表达在原发性胃癌中因 DNA 高甲基化而下调，低表达与不良临床病理特征相关。总之，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。
