Targeting B4GALT7 suppresses the proliferation, migration and invasion of hepatocellular carcinoma through the Cdc2/CyclinB1 and miR-338-3p/MMP2 pathway
Chang Liu,
Yuqi Jia,
Xinan Zhao,
Zifeng Wang,
Xiaoxia Zhu,
Chan Zhang,
Xiaoning Li,
Xuhua Zhao,
Tao Gong,
Hong Zhao,
Dong Zhang,
Yuhu Niu,
Xiushan Dong,
Gaopeng Li,
Feng Li,
Hongwei Zhang,
Li Zhang,
Jun Xu,
Baofeng Yu
Affiliations
Chang Liu
Department of Biochemistry and Molecular Biology, Changzhi Medical College, Changzhi, China
Yuqi Jia
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Xinan Zhao
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Zifeng Wang
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Xiaoxia Zhu
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Chan Zhang
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Xiaoning Li
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Xuhua Zhao
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Tao Gong
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Hong Zhao
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Dong Zhang
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Yuhu Niu
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Xiushan Dong
Department of General Surgery, Shanxi Bethune Hospital, The Third Hospital of Shanxi Medical University, Taiyuan, China
Gaopeng Li
Department of General Surgery, Shanxi Bethune Hospital, The Third Hospital of Shanxi Medical University, Taiyuan, China
Feng Li
Central Laboratory, Shanxi Cancer Hospital; Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences; Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
Hongwei Zhang
Department of Hematology, Shanxi Cancer Hospital; Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences; Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
Li Zhang
Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan, China
Jun Xu
Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan, China
Baofeng Yu
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, China
Background As a three-dimensional network involving glycosaminoglycans (GAGs), proteoglycans (PGs) and other glycoproteins, the role of extracellular matrix (ECM) in tumorigenesis is well revealed. Abnormal glycosylation in liver cancer is correlated with tumorigenesis and chemoresistance. However, the role of galactosyltransferase in HCC (hepatocellular carcinoma) is largely unknown. Methods Here, the oncogenic functions of B4GALT7 (beta-1,4-galactosyltransferase 7) were identified in HCC by a panel of in vitro experiments, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, transwell and flow cytometry assay. The expression of B4GALT7 in HCC cell lines and tissues were examined by qPCR (real-time quantitative polymerase chain reaction) and western blot assay. The binding between B4GALT7 and miR-338-3p was examined by dual-luciferase reporter assay. Results B4GALT7 encodes galactosyltransferase I and it is highly expressed in HCC cells and human HCC tissues compared with para-tumor specimens. MiR-338-3p was identified to bind the 3′ UTR (untranslated region) of B4GALT7. Highly expressed miR-338-3p suppressed HCC cell invasive abilities and rescued the tumor-promoting effect of B4GALT7 in HCC. ShRNA (short hairpin RNA) mediated B4GALT7 suppression reduced HCC cell invasive abilities, and inhibited the expression of MMP-2 and Erk signaling. Conclusion These findings identified B4GALT7 as a potential prognostic biomarker and therapeutic target for HCC.
