Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

Li, Shu; Liu, Xiaoyu; Pan, Qiu Zhong; Wu, Jian; Liu, Zhihao; Wang, Yong; Zhang, Xiaolian

doi:10.3390/v11040378

Cited by 16 publications

(14 citation statements)

References 41 publications

(45 reference statements)

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“…For example, FUT8 activates PI3K-Akt-NF- κ B signaling pathway and promotes the proliferation of HCC cells, it also stimulates the expression of drug-resistant proteins. Inhibition of FUT8 can weaken hepatocyte epidermal growth factor (EGF) and hepatocyte growth factor (HGF), and thus reduce the incidence of liver cancer [ 21 , 22 ]. miR-23a may affect the formation of N-glycochain branches on the cell surface through glucose transferase MGAT3, thereby increasing the metastasis potential of liver cancer, which provides a new idea for the mechanism of action of MGAT3 in tumor metastasis [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

B4GALT5 high expression associated with poor prognosis of hepatocellular carcinoma

Han

et al. 2022

BMC Cancer

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Background B4GALT5 is postulated to be an important protein in sugar metabolism that catalyzes the synthesis of lactosylceramide (LacCer). However, its role in hepatocellular carcinoma (HCC) remains unknown. Method We characterized the expression of B4GALT5 in HCC tissue compared to normal tissue, and explored its function of B4GALT5 in HCC by enrichment analysis based on its co-expressed gene set. Next, we checked whether B4GALT5 expression is correlated to immune infiltration level and clinical prognosis in hepatocellular carcinoma. Finally, we verified the expression of B4GALT5 using clinical samples evaluated by RT-PCR, and conducted in vitro experiments with B4GALT5-knockdown HCC cells to investigate the function of B4GALT5 in the HCC cell proliferation, migration and invasion. Results We found B4GALT5 mRNA and protein expression levels were significantly high in HCC tissue compared to normal tissue. The enrichment analysis of the gene sets that co-expressed with B4GALT5 showed specificity in HCC-related pathways and functions. Also, the expression pattern of B4GALT5 was significantly related to the immune infiltration level, especially CD4+ T cell and macrophage cells. B4GALT5 higher mRNA expression was associated with poor overall survival (OS) in HCC patients. Furthermore, In vitro experiments showed that depletion of B4GALT5 significantly inhibited HCC cell proliferation, migration and invasion. This study revealed the function and its mediated pathways of B4GALT5 in HCC, indicating that B4GALT5 may serve as a prognostic biomarker of HCC.

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Section: Discussionmentioning

confidence: 99%

B4GALT5 high expression associated with poor prognosis of hepatocellular carcinoma

Han

et al. 2022

BMC Cancer

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“…For example, FUT8 activates PI3K-Akt-NF-κB signaling pathway and promotes the proliferation of HCC cells, it also stimulates the expression of drug-resistant proteins. Inhibition of FUT8 can weaken hepatocyte epidermal growth factor (EGF) and hepatocyte growth factor (HGF), and thus reduce the incidence of liver cancer [21,22]. miR-23a may affect the formation of Nglycochain branches on the cell surface through glucose transferase MGAT3, thereby increasing the metastasis potential of liver cancer, which provides a new idea for the mechanism of action of MGAT3 in tumor metastasis [23,24].…”

Section: Discussionmentioning

confidence: 99%

B4GALT5 High Expression Associated With Poor Prognosis of Hepatocellular Carcinoma

Han

et al. 2021

Preprint

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Background: B4GALT5 is postulated to be an important protein in sugar metabolism that catalyzes the synthesis of lactosylceramide (LacCer). However, its role in hepatocellular carcinoma (HCC) remains unknown.Method: We characterized the expression of B4GALT5 in HCC tissue compared to normal tissue, and explored its function of B4GALT5 in HCC by enrichment analysis based on its co-expressed gene set. Next, we checked whether B4GALT5 expression is correlated to immune infiltration level and clinical prognosis in hepatocellular carcinoma. Finally, we verified the expression of B4GALT5 using clinical samples evaluated by RT-PCR, and conducted in vitro experiments with B4GALT5-knockdown HCC cells to investigate the function of B4GALT5 in the HCC cell proliferation, migration and invasion.Results: We found B4GALT5 mRNA and protein expression levels were significantly high in HCC tissue compared to normal tissue. The enrichment analysis of the gene sets that co-expressed with B4GALT5 showed specificity in HCC-related pathways and functions. Also, the expression pattern of B4GALT5 was significantly related to the immune infiltration level, especially CD4+ T cell and macrophage cells. B4GALT5 higher mRNA expression was associated with poor overall survival (OS) in HCC patients. Furthermore, In vitro experiments showed that depletion of B4GALT5 significantly inhibited HCC cell proliferation, migration and invasion. This study revealed the function and its mediated pathways of B4GALT5 in HCC, indicating that B4GALT5 may serve as a prognostic biomarker of HCC.

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“…Human low metastatic liver cell MHCC-97L was a gift from Prof. Fubing Wang from the Hubei Key Laboratory of Tumor Biological Behaviors of the Zhongnan Hospital of Wuhan University School of Medicine, and high metastatic liver cell HCC-LM3 was purchased from the China Center for Type Culture Collection (CCTCC) of Wuhan University, China. Human hepatocellular carcinoma cells Huh7.5.1, normal liver cells L02, MHCC-97L, and HCC-LM3 were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS, Gibco) (Invitrogen, USA) at 37°C in a 5% CO 2 atmosphere as previously described ( 20 , 21 ).…”

Section: Methodsmentioning

confidence: 99%

Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis

Kong

Chen

et al. 2022

Front. Oncol.

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Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galβ1-3/β1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC.

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Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

Cited by 16 publications

References 41 publications

B4GALT5 high expression associated with poor prognosis of hepatocellular carcinoma

B4GALT5 high expression associated with poor prognosis of hepatocellular carcinoma

B4GALT5 High Expression Associated With Poor Prognosis of Hepatocellular Carcinoma

Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis

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