ArticleMolecular cancer2022
The circular RNA circHMGB2 drives immunosuppression and anti-PD-1 resistance in lung adenocarcinomas and squamous cell carcinomas via the miR-181a-5p/CARM1 axis.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 citing papers in PubMed, 160 citations in OpenAlex.
- Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).International journal of molecular medicine · 2026Review
- Circular RNAs in NSCLC: Their Role in Tumorigenesis, Tumor Microenvironment Reshaping, and Response to Therapies.Cancers · 2026Review
- MicroRNA-181a-5p promotes papillary thyroid carcinoma progress via the PTEN/AKT pathway.Molecular biotechnology · 2026Article
- Enhancing antitumor immunity in triple-negative breast cancer through reversal of T-cell exhaustion using a CD8-targeted and membrane-camouflaged nanocarrier delivering small interfering RNA against sorting Nexin 9.Journal of nanobiotechnology · 2026Article
- Novel Insights into the Role of circRNAs in Cancer Immunotherapy Resistance and Clinical Implications.International journal of molecular sciences · 2026Review
- The PPTC7/BNIP3/NIX axis induces cGAS/STING-mediated senescence and augments CAR-T efficacy by repressing tumor-intrinsic mitophagy.Journal of experimental & clinical cancer research : CR · 2026Article
- ROS-Responsive MnOJournal of nanobiotechnology · 2026Article
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- CircIQGAP1-CARM1 axis promotes renal cell carcinoma progression through glycolytic reprogramming.Cell death & disease · 2026Article
- Deciphering the CAF‑LCN2 axis: Key to overcoming anti‑PD‑L1 immunotherapy resistance in lung cancer.International journal of molecular medicine · 2026Article
- Elevated levels of SLC38A1 are correlated with an unfavorable prognosis, as well as accelerated cell proliferation and metastasis in lung adenocarcinoma.BMC cancer · 2026Article
- Targeting c-Myc-p300-CARM1 complex induces ferroptosis and reduces CD8International journal of biological sciences · 2026Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- The potential ofJournal of thoracic disease · 2025Article
- Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy.Translational lung cancer research · 2025Review
- CircRNAs: functions and emerging roles in cancer and immunotherapy.BMC medicine · 2025Review
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- Circular RNA circLIMK1-005 promotes the progression of lung adenocarcinoma by interacting with RPA1 protein to activate CDK4 signaling.Cell death discovery · 2025Article
- LSM12 promotes the lung squamous cell carcinoma progression through mediating alternative splicing of ARRB1.Communications biology · 2025Article
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
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Abstract
backgroundPrevious studies have confirmed the oncogenic role of HMGB2 in various cancers, but the biological functions of HMGB2-derived circRNAs remain unknown. Thus, we intended to investigate the potential role of HMGB2-derived circRNAs in lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC).
methodsThe expression profiles of HMGB2-derived circRNAs in LUAD and LUSC tissues and matched normal tissues were assessed using qRT-PCR. The role of circHMGB2 in the progression of the LUAD and LUSC was determined in vitro by Transwell, CCK-8, flow cytometry and immunohistochemistry assays, as well as in vivo in an immunocompetent mouse model and a humanized mouse model. In addition, in vivo circRNA precipitation assays, luciferase reporter assays and RNA pulldown assays were performed to explore the underlying mechanism by which circHMGB2 promotes anti-PD-1 resistance in the LUAD and LUSC.
resultsThe expression of circHMGB2 (hsa_circ_0071452) was significantly upregulated in NSCLC tissues, and survival analysis identified circHMGB2 as an independent indicator of poor prognosis in the LUAD and LUSC patients. We found that circHMGB2 exerted a mild effect on the proliferation of the LUAD and LUSC cells, but circHMGB2 substantially reshaped the tumor microenvironment by contributing to the exhaustion of antitumor immunity in an immunocompetent mouse model and a humanized mouse model. Mechanistically, circHMGB2 relieves the inhibition of downstream CARM1 by sponging miR-181a-5p, thus inactivating the type 1 interferon response in the LUAD and LUSC. Moreover, we found that the upregulation of circHMGB2 expression decreased the efficacy of anti-PD-1 therapy, and we revealed that the combination of the CARM1 inhibitor EZM2302 and an anti-PD-1 antibody exerted promising synergistic effects in a preclinical model.
conclusioncircHMGB2 overexpression promotes the LUAD and LUSC progression mainly by reshaping the tumor microenvironment and regulating anti-PD-1 resistance in the LUAD and LUSC patients. This study provides a new strategy for the LUAD and LUSC treatment.
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