End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is c...End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia’s regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for addingα2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II(MAL-II)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock proteinβ8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.展开更多
Background:Bladder cancer(BLCA)is the most prevalent malignancy in the urinary tract system,while ST3GAL5 is a protein-coding gene that catalyzes the formation of ganglioside monosialodihexosylganglioside 3(GM3)syntha...Background:Bladder cancer(BLCA)is the most prevalent malignancy in the urinary tract system,while ST3GAL5 is a protein-coding gene that catalyzes the formation of ganglioside monosialodihexosylganglioside 3(GM3)synthase.GM3 synthase has been reported to significantly influence the malignant process of various cancers.However,the expression profile and functional role of ST3GAL5 specifucally in BLCA remain to be elucidated.Methods:In order to investigate the relationship between ST3GAL5 expression and malignant biological behavior and prognosis in BLCA.The mRNA expression of ST3GAL5 and clinicopathological characteristics in BLCA were firstly evaluated by public databases.Next,immunohistochemical staining was performed to analyze the protein expression of ST3GAL5 in BLCA and paracancerous tissues,as well as the expression of various types of malignant biological behavior.Subsequently,the gene set enrichment analyses(GSEA)were performed for ST3GAL5 and all correlated genes in BLCA by sorting Pearson's Correlation Coefficient.GSEA was also used to validate the pathways affected by the different expression levels of ST3GAL5 in BLCA patients.Results:The mRNA and protein expression of ST3GAL5 in BLCA were significantly higher in low-grade and non-muscle-invasive BLCA(p<0.05).The results from bioinformatics databases indicated that upregulation of ST3GAL5 have a lower grade,lower pathological stage,less susceptibility to lymphatic metastasis,and lower mortality rates.Kaplan–Meier survival analysis demonstrated that upregulation of ST3GAL5 was associated with better survival in BLCA(p<0.05).Conclusion:Upregulation of ST3GAL5 may be related to tumor suppression in BLCA,and may be a potential prognostic and therapeutic marker for BLCA.展开更多
基金supported by the National Natural Science Foundation of China(No.82370592)the Discipline Construction Project of the Health System in Pudong New Area(No.PWZbr2022-15)the Pudong New Area Special Fund for Livelihood Research Project of Science and Technology Development Fund(No.PKJ2021-Y12),China.
文摘End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia’s regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for addingα2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II(MAL-II)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock proteinβ8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.
基金Doctoral Fund Project of First Affiliated Hospital,School of Medicine,Shihezi University,China,Grant/Award Number:BS202110。
文摘Background:Bladder cancer(BLCA)is the most prevalent malignancy in the urinary tract system,while ST3GAL5 is a protein-coding gene that catalyzes the formation of ganglioside monosialodihexosylganglioside 3(GM3)synthase.GM3 synthase has been reported to significantly influence the malignant process of various cancers.However,the expression profile and functional role of ST3GAL5 specifucally in BLCA remain to be elucidated.Methods:In order to investigate the relationship between ST3GAL5 expression and malignant biological behavior and prognosis in BLCA.The mRNA expression of ST3GAL5 and clinicopathological characteristics in BLCA were firstly evaluated by public databases.Next,immunohistochemical staining was performed to analyze the protein expression of ST3GAL5 in BLCA and paracancerous tissues,as well as the expression of various types of malignant biological behavior.Subsequently,the gene set enrichment analyses(GSEA)were performed for ST3GAL5 and all correlated genes in BLCA by sorting Pearson's Correlation Coefficient.GSEA was also used to validate the pathways affected by the different expression levels of ST3GAL5 in BLCA patients.Results:The mRNA and protein expression of ST3GAL5 in BLCA were significantly higher in low-grade and non-muscle-invasive BLCA(p<0.05).The results from bioinformatics databases indicated that upregulation of ST3GAL5 have a lower grade,lower pathological stage,less susceptibility to lymphatic metastasis,and lower mortality rates.Kaplan–Meier survival analysis demonstrated that upregulation of ST3GAL5 was associated with better survival in BLCA(p<0.05).Conclusion:Upregulation of ST3GAL5 may be related to tumor suppression in BLCA,and may be a potential prognostic and therapeutic marker for BLCA.
