ArticleJournal of advanced research2024
HMGB1 promotes chemoresistance in small cell lung cancer by inducing PARP1-related nucleophagy.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 21 citations in OpenAlex.
- Therapy-related acute myeloid leukemia with a rare complex karyotype following first-line therapy for small cell lung cancer: A case report.Oncology letters · 2026Article
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- KDM4B/DHX9 promotes chemoresistance in small-cell lung cancer through the MYCN-driven signaling pathway.Oncogene · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Integrative multi-omics profiling deciphers tumor microenvironment heterogeneity and immunotherapy vulnerabilities in lung neuroendocrine carcinomas.Journal of advanced research · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- HMGB1-enhanced autophagic degradation of E-cadherin facilitates mesothelial trans-differentiation and postoperative peritoneal adhesion.BMC gastroenterology · 2025Article
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- HMGB1 downregulates DDX3 to activate the MAPK pathway, promoting the progression of colorectal cancer.Cancer gene therapy · 2025Article
- Immunotherapy for small cell lung cancer: current challenges and prospects.Experimental hematology & oncology · 2025Review
- Downregulation of KHSRP enhances carboplatin sensitivity in non-small cell lung cancer.Hereditas · 2025Article
- HMGB1 and Its Signaling Pathway in Osteosarcoma: Current Advances in Targeted Therapy.Current issues in molecular biology · 2025Review
- NRF2 promotes the migration of ovarian cancer cell lines by targeting TAGLN mediated epithelial-mesenchymal transition.Journal of ovarian research · 2025Article
- Spotlight onGenes · 2025Article
- Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis.Discover oncology · 2025Article
- Mammalian nucleophagy: process and function.Autophagy · 2025Review
- Review
- Cytoplasmic HMGB1 promotes and interacts with BECN1 through ZNF460 to induce autophagy and accelerate radioresistance in colorectal cancer cells.Frontiers in immunology · 2025Article
- Exploration of the diagnostic and prognostic roles of decreased autoantibodies in lung cancer.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSmall cell lung cancer (SCLC) is prone to chemoresistance, which is closely related to genome homeostasis-related processes, such as DNA damage and repair. Nucleophagy is the elimination of specific nuclear substances by cells themselves and is responsible for maintaining genome and chromosome stability. However, the roles of nucleophagy in tumour chemoresistance have not been investigated.
objectivesThe aim of this work was to elucidate the mechanism of chemoresistance in SCLC and reverse this chemoresistance.
methodsRNA-seq data from SCLC cohorts, chemosensitive SCLC cells and the corresponding chemoresistant cells were used to discover genes associated with chemoresistance and patient prognosis. In vitro and in vivo experiments were performed to verify the effect of high-mobility group box 1 (HMGB1) knockdown or overexpression on the chemotherapeutic response in SCLC. The regulatory effect of HMGB1 on nucleophagy was then investigated by coimmunoprecipitation (co-IP) and mass spectrometry (MS), and the underlying mechanism was explored using pharmacological inhibitors and mutant proteins.
resultsHMGB1 is a factor indicating poor prognosis and promotes chemoresistance in SCLC. Mechanistically, HMGB1 significantly increases PARP1-LC3 binding to promote nucleophagy via PARP1 PARylation, which leads to PARP1 turnover from DNA lesions and chemoresistance. Furthermore, chemoresistance in SCLC can be attenuated by blockade of the PARP1-LC3 interaction or PARP1 inhibitor (PARPi) treatment.
conclusionsHMGB1 can induce PARP1 self-modification, which promotes the interaction of PARP1 with LC3 to promote nucleophagy and thus chemoresistance in SCLC. HMGB1 could be a predictive biomarker for the PARPi response in patients with SCLC. Combining chemotherapy with PARPi treatment is an effective therapeutic strategy for overcoming SCLC chemoresistance.
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