Downregulation of ST6GAL1 Promotes Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide. The ST6 β-galactoside α-2, 6-sialyltransferase 1 (ST6GAL1) has been found aberrantly expressed in a variety of cancers including HCC, but its function and mechanism in regulating liver inflammation remain to be investigated. This study aimed to explore the role of ST6GAL1 in HCC. The data of ST6GAL1 expression, prognosis, and clinical parameters were collected and further analyzed from the public databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO). The HCC rat model was constructed by intraperitoneal injection of diethylnitrosamine. The mRNA and protein expression levels of ST6GAL1 in rat liver tissues were detected by real-time quantitative polymerase chain reaction, capillary electrophoresis, and Western blot. Results The ST6GAL1 mRNA and protein expression levels were both lower in HCC tissues compared with normal liver tissues in the public databases and HCC rat model. The survival analysis showed that upregulation of ST6GAL1 was an independent prognostic factor for good prognosis in HCC patients. The ST6GAL1 mRNA expression showed a negative correlation with ST6GAL1 methylation levels. Enrichment analysis showed that ST6GAL1 expression was most associated with metabolic, cancer, estrogen, axon guidance, cAMP, and PI3K-AKT signaling pathways. The ST6GAL1 mRNA expression negatively correlated with liver inflammation status and proportion of NK CD56bright, NK CD56dim, pDC, and CD8+ T cells in liver. Conclusion Compared with normal tissues, ST6GAL1 was lower expressed in HCC tumor tissues, and the downregulation of ST6GAL1 was associated with a poor prognosis in HCC patients. ST6GAL1 could further affect the infiltration of immune cells to exert anti-inflammation function in liver. Our study indicated that ST6GAL1 could be a potential biomarker and therapeutic target to assess the prognosis and regulate the immune cells infiltration level of HCC.

The role of N-glycosylation modification in the pathogenesis of liver cancer

“…The T cell-mediated immune response is also triggered. This conclusion can be supported by the experimental data of Liu et al [ 105 ]. The effect of N-glycosylation on the immune response is also correlated with terminal N-glycan modification.…”

Automated Capillary Electrophoresis Immunoblot for the Detection of Alpha-Synuclein in Mouse Tissue

“…Experiments utilizing this method have been conducted to evaluate protein expression in various tissues [39][40][41]. Consequently, we believe this Midbrain tissue lysates with a protein concentration of 0.2 mg/ml (A), inner ear with 0.8 mg/ml (B) and esophagus/stomach with 0.4 mg/ml (C) of 18-month-old WT C57BL/6J mice were separated by capillary electrophoresis, immobilized by UV light, and incubated with either anti-total aSyn antibody or antibody diluent.…”

Downregulation of ST6GAL2 Correlates to Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma

“…The qRT-PCR procedure and the associated kits were consistent with our previous study. 40 The gene primer sequence is listed in Table 1 .…”

“…The procedure and reagents used in this Western blot (WB) experiment were consistent with previous studies. 40 For Western blot, the protein lysates were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Epizyme Biomedical Technology, PG112, CN) and then electrophoretically transferred onto the polyvinylidene fluoride membranes (Epizyme Biomedical Technology, WJ001, CN). The antibodies utilized in this study were rabbit anti-ST6GAL2 (Proteintech, 28367-1-AP, 1:1000, US), mouse anti-GAPDH (MBL, M171-3, 1:5000, JPN), and mouse anti-β-ACTIN (Proteintech, 66009-1-Ig, 1:5000, US).…”