{
  "abstract": "Background Chronic inflammation and elevated reactive oxygen species are key contributors to hepatocellular carcinoma (HCC) progression.Objective This study aims to investigate the role of the oxidative stress sensor protein Pirin (PIR) as a critical mediator of inflammation in HCC progression.Design We investigated PIR’s role in HCC tumourigenesis through RNA interference, genetic knockout and pharmaceutical inhibition in HCC cell lines and various mouse models. Furthermore, we used transcriptomics, quantitative reverse transcription PCR, western blot, immunofluorescence staining and immunohistochemistry analysis to elucidate the molecular details.Results This study reveals a novel redox-dependent mechanism governing PIR’s nuclear shuttling, contributing to liver inflammation and HCC progression. We identified a positive feedback axis where nuclear PIR amplifies inflammatory responses, leading to hepatitis and HCC advancement. Cytokines in this loop are regulated by PIR-enhanced v-rel reticuloendotheliosis viral oncogene homolog A (RELA) transcription, promoting PIR’s nuclear translocation, increasing proinflammatory cytokine levels, and disrupting redox balance. We confirmed that liver parenchymal cells produce autocrine cytokines supporting their growth and malignancy. Notably, PIR’s redox-mediated nuclear shift can be inhibited by N-acetyl cysteine or PIR inhibitors, reducing HCC promotion in mice.Conclusion We elucidate a novel redox-dependent regulatory mechanism governing the nuclear localisation of PIR and its role in promoting liver inflammation and HCC progression. Our findings underscore the significance of cellular redox status in regulating PIR’s activity and highlight the potential of targeting this pathway with antioxidants to mitigate HCC progression.",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Huanhuan Ma"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Tingyan Cao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Fengqiong Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Dachao Sun"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Lili Chen"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Yao Lin"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Shuqing Lai"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Bin Jiang"
    },
    {
      "affiliations": [
        "Department of Gastrointestinal Oncology Surgery, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Yanming Zhou"
    },
    {
      "affiliations": [
        "Department of Gastrointestinal Oncology Surgery, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Jun You"
    },
    {
      "affiliations": [
        "Department of Gastrointestinal Oncology Surgery, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Xiyao Liu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Yue Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Furong Lin"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Yuxin Liu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Jinyang Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Weiling He"
    },
    {
      "affiliations": [
        "State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Gastrointestinal Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Qinxi Li"
    }
  ],
  "title": "Nuclear Pirin promotes HCC by acting as a key inflammation-facilitating factor",
  "uid": "6cf7d242-39d1-5071-ba19-e54ccc2f4f1a"
}