ArticleJournal of experimental & clinical cancer research : CR2024
A tumor suppressor protein encoded by circKEAP1 inhibits osteosarcoma cell stemness and metastasis by promoting vimentin proteasome degradation and activating anti-tumor immunity.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 27 citations in OpenAlex.
- An immuno-chemotherapeutic bone scaffold for tumor eradication and bone regeneration in drug-resistant osteosarcoma.Bioactive materials · 2026Article
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- PCMTD1-127aa suppresses osteosarcoma progression by competitively binding to USP10 to promoteiScience · 2026Article
- M6A-modified circArhgap26 attenuates cardiac ischemia‒reperfusion injury by suppressing plakophilin-1 palmitoylation.Signal transduction and targeted therapy · 2026Article
- CircRNAs in Immuno-Metabolic Reprogramming of Chordoma Cancer: Molecular Crosstalk and Therapeutic Potential.International journal of molecular sciences · 2026Review
- SPP1 promotes the metastasis of liver cancer cells through modulation of the MT1L/vimentin axis.American journal of cancer research · 2026Article
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- NSUN7-mediated mJournal of translational medicine · 2025Article
- m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review).International journal of molecular medicine · 2025Review
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- Recent advances in the role of circRNA in cisplatin resistance in tumors.Cancer gene therapy · 2025Review
- Role of KLF5 in enhancing ovarian cancer stemness and PARPi resistance: mechanisms and therapeutic targeting.Journal of translational medicine · 2025Article
- Research progress on N6-methyladenosine and non-coding RNA in multiple myeloma.Discover oncology · 2025Review
- A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes.Cell & bioscience · 2025Review
- Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential.Journal of hematology & oncology · 2025Review
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- Circular RNAs modulate cancer drug resistance: advances and challenges.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- circWWC3 enhances the progression of triple-negative breast cancer by interacting with vimentin to regulate the secretion of CSF2.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOsteosarcoma (OS) is one of most commonly diagnosed bone cancer. Circular RNAs (circRNAs) are a class of highly stable non-coding RNA, the majority of which have not been characterized functionally. The underlying function and molecular mechanisms of circRNAs in OS have not been fully demonstrated.
methodMicroarray analysis was performed to identify circRNAs that are differentially-expressed between OS and corresponding normal tissues. The biological function of circKEAP1 was confirmed in vitro and in vivo. Mass spectrometry and western blot assays were used to identify the circKEAP1-encoded protein KEAP1-259aa. The molecular mechanism of circKEAP1 was investigated by RNA sequencing and RNA immunoprecipitation analyses.
resultsHere, we identified a tumor suppressor circKEAP1, originating from the back-splicing of exon2 of the KEAP1 gene. Clinically, circKEAP1 is downregulated in OS tumors and associated with better survival in cancer patients. N6-methyladenosine (m6A) at a specific adenosine leads to low expression of circKEAP1. Further analysis revealed that circKEAP1 contained a 777 nt long ORF and encoded a truncated protein KEAP1-259aa that reduces cell proliferation, invasion and tumorsphere formation of OS cells. Mechanistically, KEAP1-259aa bound to vimentin in the cytoplasm to promote vimentin proteasome degradation by interacting with the E3 ligase ARIH1. Moreover, circKEAP1 interacted with RIG-I to activate anti-tumor immunity via the IFN-γ pathway.
conclusionTaken together, our findings characterize a tumor suppressor circKEAP1 as a key tumor suppressor regulating of OS cell stemness, proliferation and migration, providing potential therapeutic targets for treatment of OS.
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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.