DNA methylation is involved in the aberrant expression of miR-133b in colorectal cancer cells
DNA methylation is involved in the aberrant expression of miR-133b in colorectal cancer cells
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DNA甲基化参与结直肠癌细胞中miR-133b的异常表达
DOI：
10.3892/ol.2015.3336
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发表时间：
2015-08-01
期刊：
影响因子：
2.9
通讯作者：
Li, Xiaorong
中科院分区：
文献类型：
--
作者：
Lv, Lv;Zhou, Jianyu;Li, Xiaorong
microRNA （miRNA）表达异常与癌症密切相关。最近，许多研究表明，特定mirna的沉默与DNA甲基化有关。与健康结肠细胞相比，肌肉特异性miRNA-113b （miR-133b）在人类结直肠癌（CRC）中明显下调，并且在CRC细胞增殖和凋亡的调控中起关键作用。然而，miR-133b在结直肠癌中的下调机制尚不清楚。因此，本研究的目的是确定CRC细胞中DNA甲基化与miR-133b表达之间是否存在关联。我们发现miR-133b启动子高甲基化在结直肠癌组织中上调。为了研究miR-133b甲基化在CRC细胞中的作用，我们分析了5-aza-2'-脱氧胞苷（5-Aza-CdR）、4-苯基丁酸（PBA）和5-Aza-CdR/PBA处理的HT-29和SW620 CRC细胞的存活、细胞周期和侵袭情况。功能分析表明，去甲基化增加了miR-133b的表达，从而恢复了CRC细胞的迁移和凋亡。因此，这些结果表明miR-133b甲基化的调控可能为CRC治疗提供一种新的治疗策略。
The dysregulation of microRNA (miRNA) expression is highly involved in cancer. Recently, a number of studies have demonstrated that the silencing of specific miRNAs is associated with DNA methylation. The muscle-specific miRNA-113b (miR-133b) is markedly downregulated in human colorectal cancer (CRC) compared with healthy colon cells, and is critical in the regulation of CRC cell proliferation and apoptosis. However, the mechanism of miR-133b downregulation in CRC has yet to be elucidated. Therefore, the aim of the present study was to determine the existence of an association between DNA methylation and miR-133b expression in CRC cells. It was identified that miR-133b promoter hypermethylation is upregulated in CRC tissues. To investigate the role of miR-133b methylation in CRC cells, the survival, cell cycle and invasion were analyzed in HT-29 and SW620 CRC cells treated with 5-aza-2'-deoxycytidine (5-Aza-CdR), 4-phenylbutyric acid (PBA) and 5-Aza-CdR/PBA. Functional analysis demonstrated that demethylation increased the expression of miR-133b, which restored migration and apoptosis in CRC cells. Thus, these results indicate that the regulation of miR-133b methylation may provide a novel therapeutic strategy for CRC treatment.