title: 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.
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.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.|Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Stomatological Hospital, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Dongwang
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000067558:Biological Mimicry / Q000235:genetics; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D015820:Cadherins; D035683:MicroRNAs; D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; D000099152:Cadherin 5; C531388:MIRN27 microRNA, human; C103173:TWIST1 protein, human