MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells.
MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells.
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DOI：
10.1371/journal.pone.0088057
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Jia H;Zhang Z;Zou D;Wang B;Yan Y;Luo M;Dong L;Yin H;Gong B;Li Z;Wang F;Song W;Liu C;Ma Y;Zhang J;Zhao H;Li J;Yu J
在许多生物过程中，microRNAs作为基因表达的转录后调节因子。它们的失控常见于胃癌(GC)。虽然DNA甲基化是癌症中microRNA去调控的一个重要机制，但这一领域在很大程度上仍未被探索。从100例胃癌患者和4个胃癌细胞系的组织中提取总RNA。用TaqMan特异性探针进行实时荧光定量PCR检测miR-10a的表达水平。此外，还对miR-10a在调控细胞增殖、迁移和侵袭中的功能进行了分析。随后，用定量甲基化特异性聚合酶链式反应(QMSP)检测miR-10a上游CpG岛的DNA甲基化状态。在本研究中，我们发现miR-10a在胃癌细胞中的表达低于正常细胞，这是由于miR-10a上游的CpG岛高度甲基化所致。我们还证实了在100例胃癌患者中，miR-10a在胃癌组织中的表达略低于癌旁非肿瘤组织，并证实了部分患者miR-10a上游的CpG岛高甲基化。此外，将miR-10a重新导入GC细胞能够抑制细胞的增殖、迁移和侵袭。生物信息学和免疫印迹分析表明miR-10a在胃癌细胞中的抑瘤作用可能是通过靶向HOXA1实现的。我们的数据表明，miR-10a在GC细胞中作为肿瘤抑制因子，并在GC中被DNA高甲基化部分沉默，提示miR-10a可能是GC潜在的诊断或治疗靶点。
MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored. Total RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1. Our data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.
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