Abstract
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.
Highlights
IntroductionBy quantitative real-time PCR (qRT-PCR), were subjected to gene ontology (GO) analysis
By quantitative real-time PCR, were subjected to gene ontology (GO) analysis
MiR27a-3p was identified as a tumor suppressive miRNA in human HCC that acts by repressing vascular endothelial (VE)-cadherin and mesenchymal markers of epithelial–mesenchymal transition (EMT), which have previously been reported to be important for the function of Twist-1 in tumor metastasis and vasculogenic mimicry (VM)
Summary
By quantitative real-time PCR (qRT-PCR), were subjected to gene ontology (GO) analysis. MiR27a-3p was identified as a tumor suppressive miRNA in human HCC that acts by repressing vascular endothelial (VE)-cadherin and mesenchymal markers of EMT, which have previously been reported to be important for the function of Twist-1 in tumor metastasis and VM. These results provide additional evidence for a crucial role of miRNAs in Twist-1-mediated HCC metastasis, invasion, and VM. The expression of miR-27a-3p and its functions were extensively studied and well defined in many cancer types, the role of miR-27a-3p in human HCC and its association with Twist-1 remain unknown. We explored the molecular mechanisms underlying the function of miR-27a-3p and its potential targets
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