The mechanism study of the effect of senegenin on hepatocellular carcinoma by regulating the level of O-GlcNAc glycosylation

Hepatocellular carcinoma (HCC) is a condition with numerous etiologies and risk factors, according to the studies that are currently available. The pathogenesis of HCC remains to be studied. This study's goal was to investigate the part that senegenin and O-linked β-N-acetylglucosamineylation (O-GlcNAcylation) play in the growth and metastasis of HCC as well as the underlying molecular mechanism. Methods: We used western blot to measure O-GlcNAcylation and O-linked N-acetylglucosamine transferase (OGT) levels in HCC tissues and cells. The effects of senegenin on HCC cell proliferation and metastasis were assessed using CCK8, clonal, and transwell migration assays. We also evaluated the impact of senegenin and O-GlcNAcylation modification on pathway proteins through drug use and lentiviral infection. Results: HCC tissues and cells showed elevated OGT and O-GlcNAcylation levels. Modifying O-GlcNAcylation significantly influenced cancer cell proliferation, invasion, clonogenicity, and metastatic capacity. Senegenin treatment regulated O-GlcNAcylation, slowing HCC cell proliferation and migration, and altered Nuclear Factor kappa-light-chain-enhancer of activated B cells (NK-κB) and c-Jun N-terminal kinase (JNK) pathway protein levels involved in endoplasmic reticulum stress. Conclusion: Senegenin works by focusing on related proteins in the NK-κB and JNK pathway to lower O-GlcNAcylation levels, decrease OGT expression, and inhibit cancer cell growth and metastasis.