PeerJ (Nov 2023)

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

DOI
https://doi.org/10.7717/peerj.16450
Journal volume & issue
Vol. 11
p. e16450

Abstract

Read online Read online

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.

Keywords