miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT: an essential role for Twist-1 in HCC.
miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT: an essential role for Twist-1 in HCC.
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miR-27a-3p通过下调VE-钙粘蛋白表达和抑制EMT来抑制肿瘤转移和VM：Twist-1在HCC中的重要作用
DOI：
10.1038/srep23091
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发表时间：
2016-03-16
影响因子：
4.6
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Zhao N;Sun H;Sun B;Zhu D;Zhao X;Wang Y;Gu Q;Dong X;Liu F;Zhang Y;Li X
Twist-1和mirna已被报道与肿瘤转移和血管生成有关。然而，Twist-1与mirna之间的关系以及mirna的功能在很大程度上仍未明确。我们旨在揭示Twist-1相关的miRNA表达谱，并通过调节肝细胞癌（HCC）中miRNA的表达来确定Twist-1是否在肿瘤转移和血管生成模拟（VM）中起作用。结果显示，在Twist-1高表达的HCC细胞系和组织样本中，miR-27a-3p的表达持续下调。功能缺失和功能获得分析均显示了miR-27a-3p的抑制作用。miR-27a-3p低表达与HCC早期转移显著相关。随后的研究表明，miR-27a-3p介导了上皮-间质转化（EMT）的抑制。进一步实验表明VE-cadherin是miR-27a-3p的直接靶点，进一步证明了miR-27a-3p在抑制肿瘤转移和VM中的关键作用。结论：Twist-1在HepG2细胞中的上调导致18种mirna的差异表达。其中miR-27a-3p失调导致VM和转移。mir -27a-3p介导VE-cadherin的下调和EMT的抑制可能是Twist-1诱导肿瘤转移和VM的必要条件。我们的研究结果强调了miR-27a-3p的重要性，并提出了一种有希望的抗hcc治疗新策略。
Twist-1 and miRNAs have been reported to be associated with tumor metastasis and angiogenesis. However, the relationship between Twist-1 and miRNAs and the function of miRNAs remain largely undefined. We aimed to reveal the Twist-1-related miRNA expression profile and to determine whether Twist-1 functions in tumor metastasis and vasculogenic mimicry (VM) by regulating miRNA expression in hepatocellular carcinoma (HCC). Results showed that the expression of miR-27a-3p was consistently down-regulated in HCC cell lines and tissue samples displaying high expression of Twist-1. Both loss- and gain-of-function assays revealed suppressive effects of miR-27a-3p. Low miR-27a-3p expression was significantly associated with early metastasis in HCC. Subsequent investigations revealed that miR-27a-3p mediated the inhibition of epithelial–mesenchymal transition (EMT). Additional experiments showed that VE-cadherin is a direct target of miR-27a-3p and further demonstrated the critical role of miR-27a-3p in suppressing tumor metastasis and VM. Conclusions: Twist-1 up-regulation in HepG2 cells resulted in the differential expression of 18 miRNAs. Among them, miR-27a-3p deregulation contributed to VM and metastasis. The miR-27a-3p-mediated down-regulation of VE-cadherin and inhibition of EMT may be essential for Twist-1 to induce tumor metastasis and VM. Our findings highlight the importance of miR-27a-3p and suggest a promising new strategy for anti-HCC therapy.