B4GALNT1 Regulates Hepatocellular Carcinoma Cell Proliferation and Apoptosis via the PI3K-AKT-mTOR Pathway.

Abstract

Background: Hepatocellular carcinoma (HCC) is a ubiquitous malignancy linked to significant mortality. The abnormal expression of β-1,4-N-acetyl-galactosaminyltransferase 1 (B4GALNT1) seemed to be implicated in tumorigenesis. Nonetheless, this enzyme's roles in HCC are unclear.

Methods: By analyzing the TCGA_LIHC, GSE77509, and GSE135631 datasets, the levels of B4GALNT1 expression in HCC and surrounding non-cancerous tissues were compared. The prognostic implications of B4GALNT1 were assessed using the Cox regression analysis (CRA). The relationship of B4GALNT1 mutations with CpG island methylation levels and prognosis was examined by analyzing the cBioPortal and MethSurv databases. We sifted the evidence of B4GALNT1 expression correlating with 28 immune cell types' infiltration by harnessing the "GSVA" R package. To delve into the influences of genes associated with B4GALNT1 on HCC, we implemented gene set enrichment analysis (GSEA). We constructed a lentiviral vector expressing B4GALNT1 and knocked down B4GALNT1 in HepG2 cells. The resulting effects on HCC cell proliferation and apoptosis were analyzed via cell proliferation assays and flow cytometry.

Results: HCC tissues presented significant B4GALNT1 overexpression relative to surrounding non-cancerous tissues, marking it as a standalone risk factor for HCC progression. Methylation levels of two CpG islands were high, suggesting poor prognosis. It was detectable that B4GALNT1 expression interrelated with the infiltration extent of natural killer T cells in HCC tissues. B4GALNT1-fueled cell proliferation and enhanced resistance to apoptosis in HCC cells.

Conclusion: B4GALNT1 is a strong regulator of HCC progression and holds promise as a marker for prognosis and a hallmark for therapy in HCC.