MiR-221 mediates the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting AdipoR1
MiR-221 mediates the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting AdipoR1
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MiR-221通过靶向AdipoR1介导肝细胞癌上皮-间质转化
DOI：
10.1016/j.ijbiomac.2017.05.108
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发表时间：
2017-10-01
影响因子：
8.2
通讯作者：
Zheng, Qichang
中科院分区：
文献类型：
--
作者：
Li, Tong;Li, Min;Zheng, Qichang
最近的研究表明，miRNAs在肿瘤的发生中起着至关重要的作用。然而，它们在肝细胞癌上皮-间充质转化(EMT)中的作用还需要更好地了解。我们目前的研究表明，在肝癌组织中过表达的miR-221通过靶向一个新的基因AdipoR1来促进肝癌细胞系的EMT。首先，在40对人肝癌组织和配对的正常组织中发现了miR-221的高表达。此外，我们还发现miR-221的升高与肝细胞癌患者的临床病理特征密切相关。接下来，miR-221的丢失抑制了肝癌细胞系的EMT过程，但它的恢复增强了这一过程。此外，生物信息学软件预测，AdipoR1将成为miR-221的直接靶点。然后，我们观察到miR-221对AdipoR1蛋白表达的负调控，并通过双荧光素酶分析进一步证实了它们之间的直接结合。此外，AdipoR1基因的敲除导致肝癌细胞内EMT的促进，并且AdipoR1的过表达逆转了miR-221诱导的EMT。最后，我们发现JAK/STAT3通路可能参与了AdipoR1介导的EMT过程。总之，miR-221通过靶向AdipoR1在肝癌细胞中作为EMT过程的启动子，本研究强调了miR-221在肝癌预后和治疗中的潜在作用。(C)2017爱思唯尔B.V.保留所有权利。
Recent studies have shown that miRNAs play vital roles in tumorigenesis. However, their effects on the epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) need to be better understood. Our present study demonstrates that miR-221, which is overexpressed in HCC tissues, promotes EMT in HCC cell lines by targeting a new gene, AdipoR1. First, overexpression of miR-221 was identified in 40 pairs of human HCC tumor and matched normal tissues. Moreover, we found that elevated miR-221 was strongly associated with worse clinicopathologic features in HCC patients. Next, the loss of miR-221 inhibited, but its restoration enhanced, the EMT process in HCC cell lines. Furthermore, bioinformatics software predicted that AdipoR1 would be a direct target of miR-221. We then observed negative regulation of miR-221 on AdipoR1 protein expression, and direct binding between them was further verified using dual-luciferase assays. In addition, knockdown of AdipoR1 resulted in promotion of the EMT in HCC cells, and AdipoR1 overexpression reversed the miR-221-induced EMT. Lastly, we found that the JAK/STAT3 pathway may be involved in the AdipoR1-mediated EMT process. In conclusion, miR-221 acts as a promoter of the EMT process in HCC cells by targeting AdipoR1, and this study highlights the potential effects of miR-221 on the prognosis and treatment of HCC. (C) 2017 Elsevier B.V. All rights reserved.