Identification and functional analysis of epigenetically silenced microRNAs in colorectal cancer cells.
Identification and functional analysis of epigenetically silenced microRNAs in colorectal cancer cells.
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DOI：
10.1371/journal.pone.0020628
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ting AH
中科院分区：
文献类型：
--
作者：
Yan H;Choi AJ;Lee BH;Ting AH
微小RNA(MiRNA)的异常表达与几种人类癌症的发生和发展有关，这种失调可能是由于DNA甲基化异常引起的。虽然已知有一小部分miRNAs受DNA甲基化调控，但我们推测这种表观遗传调控更为普遍。通过结合MBD分离基因组测序(MiGs)来评估全基因组DNA甲基化模式和微阵列分析来确定miRNA的表达水平，我们系统地寻找了受DNA甲基化调控的候选miRNAs。我们发现的miRNAs在HCT116细胞中发生了强烈的甲基化；其中18个位于印迹区域，或者已经报道受到DNA甲基化的调控。在其余46个miRNAs中，有18个的表达水平与它们的DNA甲基化状态一致。经5-氮杂-2‘-脱氧胞苷处理后，有8个miRNAs表达上调，鉴定为受DNA甲基化调控的新miRNAs。此外，我们通过异位表达特定候选基因证明了这些表观遗传沉默的miRNAs的功能相关性，这导致了对癌细胞生长和迁移的抑制。除了报道这些发现，我们的研究还提供了一种可靠的、系统的策略，通过结合DNA甲基化图谱和表达数据来识别DNA甲基化调控的miRNAs。
Abnormal microRNA (miRNA) expression has been linked to the development and progression of several human cancers, and such dysregulation can result from aberrant DNA methylation. While a small number of miRNAs is known to be regulated by DNA methylation, we postulated that such epigenetic regulation is more prevalent. By combining MBD-isolated Genome Sequencing (MiGS) to evaluate genome-wide DNA methylation patterns and microarray analysis to determine miRNA expression levels, we systematically searched for candidate miRNAs regulated by DNA methylation in colorectal cancer cell lines. We found 64 miRNAs to be robustly methylated in HCT116 cells; eighteen of them were located in imprinting regions or already reported to be regulated by DNA methylation. For the remaining 46 miRNAs, expression levels of 18 were consistent with their DNA methylation status. Finally, 8 miRNAs were up-regulated by 5-aza-2′-deoxycytidine treatment and identified to be novel miRNAs regulated by DNA methylation. Moreover, we demonstrated the functional relevance of these epigenetically silenced miRNAs by ectopically expressing select candidates, which resulted in inhibition of growth and migration of cancer cells. In addition to reporting these findings, our study also provides a reliable, systematic strategy to identify DNA methylation-regulated miRNAs by combining DNA methylation profiles and expression data.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1126/science.1189123
发表时间：
2010-06-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Najafi-Shoushtari SH;Kristo F;Li Y;Shioda T;Cohen DE;Gerszten RE;Näär AM
通讯作者：
Näär AM
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
1.7
作者：
Chudin, E.;Kruglyak, S.;McDaniel, T. K.
通讯作者：
McDaniel, T. K.
影响因子：
2
作者：
Gaetje, Regine;Holtrich, Uwe;Kaufmann, Manfred
通讯作者：
Kaufmann, Manfred