Dataset Information

C-Jun-dependent ?3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering N-glycan patterns.

ABSTRACT: ?3GnT8, a key polylactosamine synthase, plays a vital role in progression of various types of human cancer. The role of ?3GnT8 in hepatocellular carcinoma (HCC) and the underlying mechanisms, however, remain largely unknown. In this study, we found that ?3GnT8 and polylactosamine were highly expressed in HCC tissues compared with those in adjacent paracancer tissues. Overexpression of ?3GnT8 promoted while knockdown of ?3GnT8 inhibited HCC cell invasion and migration in vitro. Importantly, enhanced tumorigenesis was observed in nude mice inoculated with ?3GnT8-overexpressing HCC cells, suggesting that ?3GnT8 is important for HCC development in vitro and in vivo. Mechanistically, ?3GnT8 modulated the N-glycosylation patterns of CD147 and altered the polylactosamine structures in HCC cells by physically interacting with CD147. In addition, our data showed the c-Jun could directly bind to the promoter of ?3GnT8 gene and regulate ?3GnT8 expression. ?3GnT8 regulated HCC cell invasion and migration in a C-Jun-dependent manner. Collectively, our study identified ?3GnT8 as a novel regulator for HCC invasion and tumorigenesis. Targeting ?3GnT8 may be a potential therapeutic strategy against HCC.

SUBMITTER: Liu C

PROVIDER: S-EPMC5915075 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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c-Jun-dependent β3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering <i>N</i>-glycan patterns.

Liu Chunliang C Qiu Hao H Lin Dandan D Wang Zerong Z Shi Ning N Tan Zengqi Z Liu Jun J Jiang Zhi Z Wu Shiliang S

Oncotarget 20180112 26

β3GnT8, a key polylactosamine synthase, plays a vital role in progression of various types of human cancer. The role of β3GnT8 in hepatocellular carcinoma (HCC) and the underlying mechanisms, however, remain largely unknown. In this study, we found that β3GnT8 and polylactosamine were highly expressed in HCC tissues compared with those in adjacent paracancer tissues. Overexpression of β3GnT8 promoted while knockdown of β3GnT8 inhibited HCC cell invasion and migration <i>in vitro</i>. Importantly ...[more]

PMID: 29719608

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Project description:BackgroundObesity, a major global health problem, is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent posttranslational modification, highly responsive to inflammation and ageing. The prospect of biological age reduction, by changing glycosylation patterns through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort.MethodsIgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1680 participants from the TwinsUK cohort.ResultsLow-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG N-glycome that accompanied progressive weight loss during 1-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG N-glycans (adjusted p value range 7.38 × 10-04-3.94 × 10-02). This IgG N-glycan profile is known to be associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease (adjusted p value 1.79 × 10-02) and an increase in digalactosylation (adjusted p value 5.85 × 10-06).ConclusionsAltogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced glycan and biological age.

Project description:Background: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically. Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glycosylation regulators, and annotated the modification patterns with the enrichment of immune cells and stromal cells. Considering the heterogeneity of HCC patients, the glycosylation score was constructed using single-sample gene set enrichment analysis (ssGSEA). We also explored the drugs that different HCC patients were sensitive to based on glycosylation mode and score. Results: We identified three glycosylation-regulated gene subtypes. By annotating the subtypes, it was found that the glycosylation regulated gene subtypes was highly matched with three immunophenotypes of HCC (immune-inflamed, immune-excluded, and immune-desert), regardless of the characteristics of immune cell infiltration or prognosis. Based on the characteristic genes of glycosylation-regulated gene subtypes, we constructed a glycosylation-related model, and found that glycosylation-related model was highly consistent with the glycosylation regulated gene subtypes. The glycosylation score that evaluates the glycosylation characteristics of a single HCC sample has high prognostic value, and the prognosis of patients with high glycosylation score is significantly worse. Interestingly, we found that the glycosylation score was closely related to tumor node metastasis (TNM) staging. By applying glycosylation-regulated gene subtypes and glycosylation score to explore the sensitivity of different patients to anticancer drugs, it was found that the sensitivity of Thapsigargin, Shikonin, Embelin and Epothilone. B was closely related to the glycosylation mode. Conclusion: This study reveals that the diversity of glycosylation patterns plays an important role in HCC. Therefore, evaluating the glycosylation patterns of patients with HCC will be helpful in identifying the characteristics of immune cell infiltration and selecting accurate treatment methods.

Dataset Information

C-Jun-dependent ?3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering N-glycan patterns.

Publications

c-Jun-dependent β3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering <i>N</i>-glycan patterns.

Similar Datasets

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