Targeting B4GALT7 suppresses the proliferation, migration and invasion of hepatocellular carcinoma through the Cdc2/CyclinB1 and miR-338-3p/MMP2 pathway

PeerJ. 2023 Nov 21:11:e16450. doi: 10.7717/peerj.16450. eCollection 2023.

Abstract

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: B4GALT7; MMP2; SK-Hep-1; SNU-423.

MeSH terms

  • Carcinogenesis
  • Carcinoma, Hepatocellular* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Matrix Metalloproteinase 2
  • MicroRNAs* / genetics
  • RNA, Small Interfering / genetics

Substances

  • Matrix Metalloproteinase 2
  • MicroRNAs
  • MIRN338 microRNA, human
  • MMP2 protein, human
  • RNA, Small Interfering
  • xylosylprotein 4-beta-galactosyltransferase

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 30901821, 81172136, and 82072737), the Natural Science Basic Project of Shanxi Province, China (Nos. 20210302124183, 202103021224238, 202103021224240, 201701D121165, 201801D221069, and 201901D111190), the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (No. 2021L339), the Scientific Research Starting Foundation for Doctor of Changzhi Medical College (No. BS202007), the Research Project Supported by Shanxi Scholarship Council of China (Nos. 2020-194, and 2021-165), the Open Fund from Key Laboratory of Cellular Physiology (Shanxi Medical University), the Ministry of Education, China (No. KLMEC/SXMU-202011, CPOF202301), the Shanxi ‘1331 Project’ Key Subjects Construction, China (No. 1331KSC), the Outstanding Youth Foundation of Shanxi Province, China (No. 201901D211547), the Scientific research project of Shanxi Provincial Health Commission, China (No. 2019059), and the “136” College-level open fund, China (No. 2021YZ03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.