ArticleCancer communications (London, England)2023
HMMR alleviates endoplasmic reticulum stress by promoting autophagolysosomal activity during endoplasmic reticulum stress-driven hepatocellular carcinoma progression.
Article in Cancer communications (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 28 citations in OpenAlex.
- Epigenetic Silencing of CYYR1 Promotes Lung Adenocarcinoma Progression Through TRIM21-Dependent Regulation of HMMR Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Identification of telomere-related gene signatures for immune cell infiltration and prognosis in hepatocellular carcinoma.Translational cancer research · 2026Article
- Diverse Forms of Autophagy and Their Roles in Liver Disease and Aging: A Comprehensive Review.Proteomes · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Endothelial cells secrete small extracellular vesicles to promote neuron endoplasmic reticulum stress injury via miR-146a-5p/Eif4g2 axis in ischemic stroke.Journal of advanced research · 2026Article
- Lactylation-drived TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt/β-catenin pathway.Cell death & disease · 2026Article
- Article
- Liver-specific gene therapy based on self-complementary adeno-associated virus for lysosomal acid lipase deficiency.Frontiers in pharmacology · 2026Article
- Identifying key genes involved in HBV-related hepatocellular carcinoma: diagnose, prognosis, interaction and immune analysis.Discover oncology · 2025Article
- Investigating Liquid-Liquid Phase Separation in Lung Adenocarcinoma to Improve Prognostic Accuracy and Treatment Efficacy.Journal of cellular and molecular medicine · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Ubiquitination in hepatocellular carcinoma immunity.Journal of translational medicine · 2025Review
- Effects of ER-phagy regulatory genes on the microenvironment of hepatocellular carcinoma: a comprehensive analysis.Discover oncology · 2025Article
- HBV activates hepatic stellate cells through RUNX2/ITGBL1 axis.Virology journal · 2025Article
- The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- In vitro analysis of the molecular mechanisms of ursolic acid against ovarian cancer.BMC complementary medicine and therapies · 2025Article
- Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells.Toxics · 2025Article
- Bioinformatics and system biology approach to discover the common pathogenetic processes between COVID-19 and chronic hepatitis B.PloS one · 2025Article
- NInternational journal of biological sciences · 2025Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe mechanism of hepatitis B virus (HBV)-induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan-mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development.
methodsAn HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues.
resultsWe found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues.
conclusionsThis study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV-related carcinogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.