ArticleFrontiers in oncology2022
Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 19 citations in OpenAlex.
- Ubiquitin signaling in tumor-associated macrophage reprogramming: mechanisms and therapeutic opportunities in cancers.Biomarker research · 2026Review
- DTX3 promotes anti-tumor immunity by inducing PD-L1 ubiquitination and is suppressed by p65/miR-222 in bladder cancer.Oncogene · 2026Article
- RNF125 mediates the anti-breast cancer activity of betulinic acid through ubiquitin-dependent degradation of MYH9.International journal of clinical oncology · 2026Article
- RNF125 promotes CD8 T cell-mediated anticancer immunity and suppresses the malignant phenotype of cervical cancer.Molecular and cellular biochemistry · 2026Article
- IL-7Rα signaling potentiates the anti-tumor activity of NK92 cells.Frontiers in immunology · 2026Article
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Ubiquitination-based Classification and a Prognostic Signature Identify the Role of TRIM21 in Sarcoma Progression.Current medicinal chemistry · 2026Article
- Targeting mTORC2-dependent AKT/FOXO1/RNF125 signaling exploits a therapeutic vulnerability in c-MET-activated and β-catenin-mutated hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2025Article
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- The enigma of the RING-UIM E3 ligases: its transformative impact on cancer research.Journal of translational medicine · 2025Review
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125.Oncology reports · 2025Article
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Identifying Common Diagnostic Biomarkers and Therapeutic Targets between COPD and Sepsis: A Bioinformatics and Machine Learning Approach.International journal of chronic obstructive pulmonary disease · 2025Article
- Upregulation ofGenes · 2024Article
- DNA methylation biomarker panels for differentiating various liver adenocarcinomas, including hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and pancreatic adenocarcinoma liver metastases.Clinical epigenetics · 2024Article
- Posttranslational regulatory mechanism of PD-L1 in cancers and associated opportunities for novel small-molecule therapeutics.Acta biochimica et biophysica Sinica · 2024Review
- A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma.Scientific reports · 2024Article
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy.
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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.