ArticleNeuro-oncology2021
Rolling-translated EGFR variants sustain EGFR signaling and promote glioblastoma tumorigenicity.
Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
85 citing papers in PubMed, 126 citations in OpenAlex.
- Functions of exosome-derived noncoding RNA-encoded polypeptides/proteins in human diseases.Genes & diseases · 2027Review
- Circular RNAs in NSCLC: Their Role in Tumorigenesis, Tumor Microenvironment Reshaping, and Response to Therapies.Cancers · 2026Review
- MAPT-derived circTau6 induces tau pathogenesis and neurodegeneration by encoding Tau variants.Molecular psychiatry · 2026Article
- The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.Medical oncology (Northwood, London, England) · 2026Review
- Circular RNA as emerging precision therapeutics: from RNA regulation to peptide translation.Precision clinical medicine · 2026Review
- Plant Peptides on the Rise: From Historical Insight to Future Applications.Plant biotechnology journal · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- Crosstalk between circRNAs and the MAPK signaling pathway in cancer progression.Discover oncology · 2026Review
- Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development.Experimental & molecular medicine · 2026Review
- Liu Wei formula ameliorates EGFR-induced malignant glioma progression by regulating EGFR/PI3K/AKT pathway and T-cell antitumor immunity.Frontiers in pharmacology · 2026Article
- CircZFAND6 suppresses gastric cancer metastasis and reduces resistance to TKI therapy.Molecular cancer · 2025Article
- circ-EGFR is a predictor of response to Cetuximab and a potential target in colorectal cancer.EMBO molecular medicine · 2025Article
- Unveiling the Role of circRNAs in Pyroptotic Signalling: From Molecular Crosstalk to Disease Modulation.Journal of cellular and molecular medicine · 2025Review
- Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review).International journal of oncology · 2025Review
- METTL3 facilitates the translation of CircSIK2 during chicken myogenesis in an m6A dependent manner.PLoS genetics · 2025Article
- Regulatory roles of circular RNAs in Wnt and other oncogenic signaling pathways in breast cancer progression: a comprehensive review.European journal of medical research · 2025Review
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5.Journal of experimental & clinical cancer research : CR · 2025Article
- tRNA-Derived Small RNA Accelerates Tumorigenesis through Crosstalk with Tumor-Associated Macrophages, and Downregulation with Cell Membrane-Modified Polymer Nanoparticles Enables Treatment Response.ACS applied materials & interfaces · 2025Article
- Collaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant epidermal growth factor receptor (EGFR) activation is observed in over 50% of cases of adult glioblastoma (GBM). Nevertheless, EGFR antibodies are ineffective in clinical GBM treatment, suggesting the existence of redundant EGFR activation mechanisms. Whether circular RNA (circRNA) encodes a protein involved in EGFR-driven GBM remains unclear. We reported an unexpected mechanism in which circular EGFR RNA (circ-EGFR) encodes a novel EGFR variant to sustained EGFR activation.
methodWe used RNA-seq, Northern blot, and Sanger sequencing to confirm the existence of circ-EGFR. Antibodies and a liquid chromatograph tandem mass spectrometer were used to identify circ-EGFR protein products. Lentivirus-transfected stable cell lines were used to assess the biological functions of the novel protein in vitro and in vivo. Clinical implications of circ-EGFR were assessed using 97 pathologically diagnosed GBM patient samples.
resultsThe infinite open reading frame (iORF) in circ-EGFR translated repeating amino acid sequences via rolling translation and programmed -1 ribosomal frameshifting (-1PRF) induced out-of-frame stop codon (OSC), forming a polymetric novel protein-complex, which we termed rolling-translated EGFR (rtEGFR). rtEGFR directly interacted with EGFR, maintained EGFR membrane localization and attenuated EGFR endocytosis and degradation. Importantly, circ-EGFR levels correlated with the EGFR signature and predicted the poor prognosis of GBM patients. Deprivation of rtEGFR in brain tumor-initiating cells (BTICs) attenuated tumorigenicity and enhanced the anti-GBM effect.
conclusionOur findings identified the endogenous rolling-translated protein and provided strong clinical evidence that targeting rtEGFR could improve the efficiency of EGFR-targeting therapies in GBM.
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Registered trials
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.