Inhibitions of Epithelial to Mesenchymal Transition and Cancer Stem Cells-Like Properties Are Involved in miR-148a-Mediated Anti-Metastasis of Hepatocellular Carcinoma
Inhibitions of Epithelial to Mesenchymal Transition and Cancer Stem Cells-Like Properties Are Involved in miR-148a-Mediated Anti-Metastasis of Hepatocellular Carcinoma
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DOI：
10.1002/mc.22064
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发表时间：
2014-12-01
影响因子：
4.6
通讯作者：
Zhang, Jianping
中科院分区：
文献类型：
--
作者：
Yan, Han;Dong, Xiaogang;Zhang, Jianping
上皮间质转化（EMT）和癌症干细胞（CSC）样特性的获得是肝细胞癌（HCC）转移和术后复发的重要步骤。然而，所涉及的分子机制仍然不清楚。通过 miRNA 微阵列分析确定，相对于高分化 HCC 组织，低分化 HCC 组织中 miR-148a 的表达较低。选择MHCC97H和MHCC97L（具有迁移能力的HCC细胞）以及具有不同分化状态的HCC组织进行进一步研究。结果显示miR-148a水平与HCC组织的分化状态呈负相关。在 MHCC97H 和 MHCC97L 细胞中，miR-148a 的过度表达会阻断 EMT 过程，减弱 CD90 和 CD44（肝癌干细胞的生物标志物）的表达，并抑制其迁移能力。通过 TargetScan 和算法，预测 miR-148a 会与 Wnt1 mRNA 3-UTR 结合。 Wnt1 被证实是 HCC 细胞中 miR-148a 的靶基因，并且确定 Wnt 信号通路参与 miR-148a 介导的 MHCC97H 细胞 EMT 和 CSCs 样特性的抑制。此外，miR-148a在非转移性HCC组织中的表达高于转移性HCC组织。结果表明，miR-148a 通过影响 Wnt 信号通路，阻断 EMT 和 CSC 样特性，从而抑制 HCC 转移。 (c) 2013 年 Wiley 期刊公司。
The epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cells (CSCs)-like properties are essential steps in the metastasis and postsurgical recurrence of hepatocellular carcinomas (HCCs). The molecular mechanisms involved, however, remain obscure. As determined by an miRNA microarray analysis, there was lower expression of miR-148a in poorly differentiated HCC tissues relative to well-differentiated HCC tissues. MHCC97H and MHCC97L (HCC cells with migratory capacity) and HCC tissues with various differentiation status were selected for further investigation. The results showed that miR-148a levels inversely correlated with the differentiation status of HCC tissues. In MHCC97H and MHCC97L cells, over-expression of miR-148a blocked the EMT process, attenuated the expression of CD90 and CD44 (biomarkers for liver cancer stem cells), and inhibited their migratory capacity. Via TargetScan and algorithms, miR-148a was predicted to bind to the Wnt1 mRNA 3-UTR. Wnt1 was confirmed as a target gene of miR-148a in HCC cells, and the Wnt signal pathway was determined to be involved in the miR-148a-mediated inhibition of EMT and CSCs-like properties of MHCC97H cells. Moreover, the expression of miR-148a in nonmetastatic HCC tissues was higher than that in metastatic HCC tissues. The results suggest that miR-148a inhibits the metastasis of HCCs by blocking EMT and CSCs-like properties through effects on the Wnt signaling pathway. (c) 2013 Wiley Periodicals, Inc.