title: The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial-Mesenchymal Transition.
abstract: The transcription factor Runx2 has been reported to promote epithelial-mesenchymal transition (EMT) in many tumors. Vasculogenic mimicry (VM) is described as the mimicry of endothelial cells by tumor cells to form microvascular tubes in aggressive tumors. Galectin-3 has been reported to regulate cell invasion, migration, and VM formation; it could be regulated by Runx2. However, the relationship between Runx2, Galectin-3, EMT, and VM has not been studied in hepatocellular carcinoma (HCC). We examined Runx2 expression in 89 human HCC samples and found Runx2 expression was associated with VM. Clinical-pathological data analysis revealed that Runx2 expression was associated with a shorter survival period. Overexpression of Runx2 promoted EMT and enhanced cell migration, invasion, and VM formation in HepG2 cells. Conversely, the downregulation of Runx2 inhibited EMT and reduced cell invasion, migration, and VM formation in SMMC7721. Galectin-3 expression declined following the downregulation ofRunx2in HepG2 cells, and increased in SMMC7721 cells afterRunx2knockdown. We consistently demonstrated that the downregulation ofLGALS3in HepG2-Runx2 cells reduced cell migration; invasion and VM formation; while upregulation ofLGALS3in SMMC7721-shRunx2 cells enhanced cell migration, invasion, and VM formation. The results indicate that Runx2 could promote EMT and VM formation in HCC and Galectin-3 might have some function in this process.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. imcaozi@163.com.
authors.forename: Zi
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. baocunsun@aliyun.com.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China. baocunsun@aliyun.com.|Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China. baocunsun@aliyun.com.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. xiulanzhao@aliyun.com.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China. xiulanzhao@aliyun.com.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China. Yanhuizhang015@163.com.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. wyft1022@163.com.|Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China. wyft1022@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. liangxiaohui123@126.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. dxy7235202@126.com.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. zhaonantj@tmu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011379:Prognosis; D034622:RNA Interference; D047368:Tumor Burden
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D037502:Galectin 3
keywords: Galectin-3; Runx2; epithelial-mesenchymal transition; hepatocellular carcinoma; portal vein invasion; vasculogenic mimicry