The critical role of B4GALT4 in promoting microtubule spindle assembly in HCC through the regulation of PLK1 and RHAMM expression

Abstract Beta 1,4‐galactosyltransferase (B4GALT)‐family glycosyltransferases are involved in multiple biological processes promoting cancer progression, regulating the dynamic network of cancer cell proliferation and apoptosis, and are associated with metastasis. However, their roles in the dysregulation of expressions and functions in hepatocellular carcinoma (HCC) remain unclear. Herein, bioinformatic approaches have been applied to investigate their expression profiles, and to obtain correlations between gene expressions and clinicopathological parameters as well as downstream target genes in HCC. Multiple databases were used to screen the expressions of B4GALT family members in tumor tissues, and to evaluate their prognostic value among HCC patients in different aspects. Results indicated an overall upregulation of B4GALTs' transcription levels in tumor tissues and a strong correlation with poor prognosis. Through Gene Ontology analysis, gene set enrichment analysis, and verification of single‐cell RNA sequencing data, we established a connection between the B4GALT family and microtubule spindle assembly, which particularly highlighted the role of B4GALT4 in this phenomenon. B4GALT4 knockdown downregulated the production of lumican, and repressed the expressions of polo‐like kinase 1 and RHAMM by regulating the transforming growth factor‐beta pathway, thus suggesting that B4GALT4 is a critical promotor for HCC. We believe that these studies will provide valuable insight into the role of B4GALT family members in HCC and lead to the development of new strategies to improve the outcomes for patients with HCC.