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.
Gut (BMJ) published a clinical update in Research Highlights on 07 Apr 2026.
The item focuses on Nuclear Pirin promotes HCC by acting as a key inflammation-facilitating factor.
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