MiR-107 suppresses proliferation of hepatoma cells through targeting HMGA2 mRNA 3′UTR
MiR-107 suppresses proliferation of hepatoma cells through targeting HMGA2 mRNA 3′UTR
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DOI：
10.1016/j.bbrc.2016.10.070
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发表时间：
2016-11-18
影响因子：
3.1
通讯作者：
Zhang, Xiaodong
中科院分区：
文献类型：
--
作者：
Wang, Yuan;Chen, Fuquan;Zhang, Xiaodong
背景与目的：miR-107的异常表达参与多种人类癌症的发生发展。然而，miR-107在肝细胞癌（HCC）中的作用并没有很好的文献记载。在本研究中，我们旨在探讨miR-107在肝癌发生中的功能。方法：应用生物信息学分析预测miR-107的靶基因。荧光素酶报告基因检测验证miR-107在高迁移率组A2 (HMGA2) mRNA 3'-非翻译区（3' utr）的结合位点。采用qRT-PCR和Western blot检测mRNA和蛋白的表达水平。功能上，采用MTT和EdU法进行增殖分析。临床收集30例HCC标本及相应的瘤周肝组织。结果：生物信息学分析显示miR-107可能靶向HMGA2 mRNA 3'UTR。荧光素酶报告基因检测证实miR-107结合位点位于HMGA2 mRNA的3'UTR中。此外，miR-107可以在mRNA和蛋白水平上以剂量依赖性的方式下调HMGA2。有趣的是，miR-107可以抑制肝癌细胞的增殖，而anti - miR-107可以促进细胞的增殖，而这种增殖被HMGA2的干扰所阻断。在临床上，相对于肿瘤周围的肝组织，miR-107在HCC样本中较低。HCC样品中miR-107的表达水平与HMGA2 mRNA的表达水平呈负相关。结论：MiR-107通过靶向HMGA2 mRNA抑制肝癌细胞增殖。我们的发现为肝癌的发生机制提供了新的见解。(C) 2016 Elsevier Inc.版权所有。
Background and aim: Aberrant expression of miR-107 is involved in the development of several human cancers. However, the role of miR-107 in hepatocellular carcinoma (HCC) is not well documented. In the present study, we aim to explore the function of miR-107 in hepatocarcinogenesis.Methods: Bioinformatics analysis was applied to predict the target genes of miR-107. Luciferase reporter gene assay was performed to verify the miR-107 binding sites in 3'-untranslated region (3'UTR) of high mobility group A2 (HMGA2) mRNA. The expression levels of mRNA and protein were examined using qRT-PCR and Western blot analysis. Functionally, MTT and EdU assays were carried out for proliferation analysis. Clinically, thirty HCC samples and their corresponding peritumor liver tissues were collected.Results: Bioinformatics analysis revealed that miR-107 might target HMGA2 mRNA 3'UTR. Luciferase reporter gene assays verified that the miR-107 binding site was located in the 3'UTR of HMGA2 mRNA. Furthermore, miR-107 could down-regulate HMGA2 at the levels of mRNA and protein in a dose dependent manner. Interestingly, miR-107 inhibited the proliferation of hepatoma cells, while antimiR-107 could promote the cell proliferation, which was blocked by the interference of HMGA2. Clinically, miR-107 was lower in HCC samples relative to peritumor liver tissues. The expression levels of miR-107 were negatively correlated with those of HMGA2 mRNA in HCC samples.Conclusion: MiR-107 suppresses the proliferation of hepatoma cells by targeting HMGA2 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. (C) 2016 Elsevier Inc. All rights reserved.