Upregulated expression of miR-106a by DNA hypomethylation plays an oncogenic role in hepatocellular carcinoma
Upregulated expression of miR-106a by DNA hypomethylation plays an oncogenic role in hepatocellular carcinoma
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DNA 低甲基化导致 miR-106a 表达上调，在肝细胞癌中发挥致癌作用
DOI：
10.1007/s13277-014-2945-2
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Hu, Hao
中科院分区：
文献类型：
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作者：
Yuan, Renshun;Zhi, Qiaoming;Hu, Hao
microRNA（miRNA）的异常表达已被广泛认为在包括肝细胞癌（HCC）在内的多种癌症中起着极其重要的作用。根据以往的研究，miR-106 a的异常表达与多种肿瘤的发生密切相关。然而，miR-106 a在HCC中的表达仍不清楚。本研究首先检测了36对HCC组织中miR-106 a的表达水平。结果显示，miR-106 a在肝癌组织中的表达明显高于癌旁组织。采用实时定量PCR（qPCR）和BSP技术检测肝癌细胞系中miR-106 a的表达和启动子甲基化。结论是miR-106 a启动子区域的甲基化状态与miR-106 a的表达呈负相关。通过在线软件预测后，进一步采用双荧光素酶报告基因检测法确定TP 53 INP 1和CDKN 1A可能是miR-106 a的直接靶点。最后，我们在体外研究了miR-106 a在肝癌细胞中的作用。结果表明，高miR-106 a表达的细胞株比低miR-106 a表达的细胞株具有更强的侵袭力、更快的细胞周期进程和更强的抗凋亡能力。因此，我们的研究表明，miR-106 a通过其启动子低甲基化而上调表达可能有助于HCC的进展，这可能被认为是未来潜在的有效生物标志物和治疗方法。
Aberrant microRNA (miRNA) expression has been widely recognized to play an extremely important role in several cancers, including hepatocellular carcinoma (HCC). According to the previous studies, abnormal miR-106a expression was closely related to various cancer occurrences. However, the miR-106a expression in HCC remains unclear. In our study, we firstly detected the miR-106a expression levels in 36 pairs of HCC tissues. The results showed that miR-106a expression in HCC tissues was apparently higher than the level in the adjacent tissues. Then, we used quantitative real-time PCR (qPCR) and BSP to analyze miR-106a expression and promoter methylation in HCC cell lines. There came to a conclusion that the methylation status of the miR-106a promoter region was inversely correlated with the expression of miR-106a. After prediction with online software, we further used dual-luciferase reporter gene assay to ensure that TP53INP1 and CDKN1A might be the direct targets of miR-106a. At last, we explored the functions of miR-106a in HCC cells in vitro. Our results manifested that high-miR-106a cell line had stronger invasiveness, faster cell cycle progression, and more resistance to apoptosis compared with the low-miR-106a cell line. Therefore, our study suggested that upregulated expression of miR-106a by its promoter hypomethylation might contribute to the progression of HCC, which might be considered as a potentially effective biomarker and therapeutic approach in the future.