Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma
BackgroundHepatitis B virus-related hepatocarcinogenesis (HBV-related HCC) involves a variety of causes including oncogene hypomethylation, oxidative stress and HBV itself. Oxidative stress induces an alternation in the DNA methylation status. We aimed to study the relationship between oxidative str...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1590492/full |
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| author | Jing-Wen Wang Han-Xu Zhu Feng Zhang He Wang Yu-Chen Fan Yu-Chen Fan Li-Yan Han Kai Wang Kai Wang |
| author_facet | Jing-Wen Wang Han-Xu Zhu Feng Zhang He Wang Yu-Chen Fan Yu-Chen Fan Li-Yan Han Kai Wang Kai Wang |
| author_sort | Jing-Wen Wang |
| collection | DOAJ |
| description | BackgroundHepatitis B virus-related hepatocarcinogenesis (HBV-related HCC) involves a variety of causes including oncogene hypomethylation, oxidative stress and HBV itself. Oxidative stress induces an alternation in the DNA methylation status. We aimed to study the relationship between oxidative stress and murine double minute-2 (MDM2) methylation status in HBV-related HCC patients and healthy controls (HCs).MethodsA total of 135 patients with HBV-related HCC and 26 healthy controls (HCs) were recruited. The MDM2 methylation status was detected by methylation-specific PCR. The expression of MDM2 mRNA was assessed using quantitative real-time PCR. The plasma malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nuclear factor erythroid 2-related factor 2 (NRF2), heme Oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) were measured by enzyme-linked immunosorbent assay (ELISA). Thirty-six patients with HBV-related HCC and 11 HCs were selected and the serum metabolism was analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS).ResultsCompared with HCs, the MDM2 promoter methylation frequency was significantly decreased in HBV-related HCC. The MDA levels were increased, whereas the GSH, SOD, NRF2, HO-1, and GPX4 levels were decreased in the HBV-related HCC patients relative to HCs. There were 216 differential metabolites between HBV-related HCC and HCs in plasma, which belongs to amino acids, bile acids, fatty acids, phospholipids, and other compounds. The cysteine and methionine metabolism were the most significant metabolic pathways associated with differential metabolites between MDM2 methylated group and MDM2 unmethylated group in HBV-related HCC.ConclusionOur results suggested that oxidative stress may cause MDM2 hypomethylation, in which cysteine and methionine pathway might play an important role in. |
| format | Article |
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| institution | DOAJ |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-df7f4557be4e4a5aacf3b0075c0d2de12025-08-20T02:57:44ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-05-011610.3389/fmicb.2025.15904921590492Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinomaJing-Wen Wang0Han-Xu Zhu1Feng Zhang2He Wang3Yu-Chen Fan4Yu-Chen Fan5Li-Yan Han6Kai Wang7Kai Wang8Department of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaInstitute of Hepatology, Shandong University, Jinan, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, ChinaInstitute of Hepatology, Shandong University, Jinan, ChinaBackgroundHepatitis B virus-related hepatocarcinogenesis (HBV-related HCC) involves a variety of causes including oncogene hypomethylation, oxidative stress and HBV itself. Oxidative stress induces an alternation in the DNA methylation status. We aimed to study the relationship between oxidative stress and murine double minute-2 (MDM2) methylation status in HBV-related HCC patients and healthy controls (HCs).MethodsA total of 135 patients with HBV-related HCC and 26 healthy controls (HCs) were recruited. The MDM2 methylation status was detected by methylation-specific PCR. The expression of MDM2 mRNA was assessed using quantitative real-time PCR. The plasma malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nuclear factor erythroid 2-related factor 2 (NRF2), heme Oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) were measured by enzyme-linked immunosorbent assay (ELISA). Thirty-six patients with HBV-related HCC and 11 HCs were selected and the serum metabolism was analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS).ResultsCompared with HCs, the MDM2 promoter methylation frequency was significantly decreased in HBV-related HCC. The MDA levels were increased, whereas the GSH, SOD, NRF2, HO-1, and GPX4 levels were decreased in the HBV-related HCC patients relative to HCs. There were 216 differential metabolites between HBV-related HCC and HCs in plasma, which belongs to amino acids, bile acids, fatty acids, phospholipids, and other compounds. The cysteine and methionine metabolism were the most significant metabolic pathways associated with differential metabolites between MDM2 methylated group and MDM2 unmethylated group in HBV-related HCC.ConclusionOur results suggested that oxidative stress may cause MDM2 hypomethylation, in which cysteine and methionine pathway might play an important role in.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1590492/fullHBV-related hepatocellular carcinomamurine double minute-2oxidative stressDNA methylationmetabolomics |
| spellingShingle | Jing-Wen Wang Han-Xu Zhu Feng Zhang He Wang Yu-Chen Fan Yu-Chen Fan Li-Yan Han Kai Wang Kai Wang Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma Frontiers in Microbiology HBV-related hepatocellular carcinoma murine double minute-2 oxidative stress DNA methylation metabolomics |
| title | Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma |
| title_full | Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma |
| title_fullStr | Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma |
| title_full_unstemmed | Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma |
| title_short | Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma |
| title_sort | reduced murine double minute 2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus related hepatocellular carcinoma |
| topic | HBV-related hepatocellular carcinoma murine double minute-2 oxidative stress DNA methylation metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1590492/full |
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