ArticleJournal for immunotherapy of cancer2023
Hsa-LINC02418/mmu-4930573I07Rik regulated by METTL3 dictates anti-PD-L1 immunotherapeutic efficacy via enhancement of Trim21-mediated PD-L1 ubiquitination.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- DTX3 promotes anti-tumor immunity by inducing PD-L1 ubiquitination and is suppressed by p65/miR-222 in bladder cancer.Oncogene · 2026Article
- The lncRNA-m6A axis in cancer: a bidirectional regulatory network in tumor progression and therapeutic resistance.Journal of translational medicine · 2026Review
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Research progress on long non‑coding RNAs in lung cancer (Review).Molecular medicine reports · 2026Review
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Tumor-immune crosstalk in lung cancer: emerging roles of long non-coding RNAs.Frontiers in immunology · 2026Review
- Roles and potential applications of non-coding RNAs in cancer treatment with immune checkpoint inhibitors and immunomodulatory therapies.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- TRIM family proteins: dual roles in tumor immunity.Frontiers in cell and developmental biology · 2026Review
- The role of m6A modification in non-small cell lung cancer: functional insights and impact on therapy resistance.Cancer cell international · 2025Review
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- TRIM21 promotes colorectal cancer development through regulating DNA replication by TCF3/MCM2/5 axis.Cell death discovery · 2025Article
- Potential regulatory role of the mActa biochimica et biophysica Sinica · 2025Review
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer.Cell proliferation · 2025Review
- Interactions between long non-coding RNAs and m6 A modification in cancer.Discover oncology · 2025Review
- Advanced pathological subtype classification of thyroid cancer using efficientNetB0.Diagnostic pathology · 2025Article
- Targeting the TRIM21-PD-1 axis potentiates immune checkpoint blockade and CAR-T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes.Cell & bioscience · 2025Review
- Cis-Regulation of an mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLimited response to programmed death ligand-1 (PD-L1)/programmed death 1 (PD-1) immunotherapy is a major hindrance of checkpoint immunotherapy in non-small cell lung cancer (NSCLC). The abundance of PD-L1 on the tumor cell surface is crucial for the responsiveness of PD-1/PD-L1 immunotherapy. However, the negative control of PD-L1 expression and the physiological significance of the PD-L1 inhibition in NSCLC immunotherapy remain obscure.
methodsBioinformatics analysis was performed to profile and investigate the long non-coding RNAs that negatively correlated with PD-L1 expression and positively correlated with CD8+T cell infiltration in NSCLC. Immunofluorescence,
resultsLINC02418 is a negative regulator of PD-L1 expression that positively correlated with CD8+T cell infiltration, predicting favorable clinical outcomes for patients with NSCLC. LINC02418 downregulates PD-L1 expression by enhancing PD-L1 ubiquitination mediated by E3 ligase Trim21. Both hsa-LINC02418 and mmu-4930573I07Rik (its homologous RNA in mice) regulate PD-L1 therapeutic efficacy in NSCLC via Trim21, inducing T cell-induced apoptosis
conclusionLINC02418 functions as a negative regulator of PD-L1 expression in NSCLC cells by promoting the degradation of PD-L1 through the ubiquitin-proteasome pathway. The expression of LINC02418 is regulated by METTL3/YTHDF2-mediated m6A modification. This study illuminates the underlying mechanisms of PD-L1 negative regulation and presents a promising target for improving the effectiveness of anti-PD-L1 therapy in NSCLC.
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