ArticleGenome biology2021
A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 172 citations in OpenAlex.
- Glasdegib in combination with temozolomide and radiotherapy in adult patients with newly diagnosed glioblastoma: the phase Ib/II GEINO 1602 trial.Nature communications · 2025Trial
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.Medical oncology (Northwood, London, England) · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development.Experimental & molecular medicine · 2026Review
- Comprehensive analysis of differential mRNA, lncRNA and circRNA and their ceRNA network in the Longissimus Dorsi Muscle of Jerseyyak in response to dietary protein levels.Frontiers in veterinary science · 2026Article
- Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review).International journal of oncology · 2025Review
- Circular RNA circFTO promotes pressure overload-induced cardiac hypertrophy by encoding a novel protein FTO-36aa.Journal of thoracic disease · 2025Article
- Brain transcriptomics highlight abundant gene expression and splicing alterations in non-neuronal cells in aFTLD-U.Acta neuropathologica · 2025Article
- Multimodal zero-shot learning of previously unseen epitranscriptomes from RNA-seq data.Briefings in bioinformatics · 2025Article
- Coding circular RNA in human cancer.Genes & diseases · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- Circular RNAs in neurological conditions - computational identification, functional validation, and potential clinical applications.Molecular psychiatry · 2025Review
- Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential.Journal of hematology & oncology · 2025Review
- The protein circPETH-147aa regulates metabolic reprogramming in hepatocellular carcinoma cells to remodel immunosuppressive microenvironment.Nature communications · 2025Article
- Circular RNA-Encoded Proteins in Disease Pathogenesis.International journal of biological sciences · 2025Review
- Circular RNAs: history, metabolism, mechanisms of function, and regulatory roles at a glance.Annals of medicine and surgery (2012) · 2025Review
- Utilization of artificial circular RNAs as miRNA sponges and anti-PD-1 scFv expression platforms to suppress hepatocellular carcinoma progression.Frontiers in immunology · 2025Article
- Regulatory role of circular RNAs in the development of therapeutic resistance in the glioma: A double-edged sword.Iranian journal of basic medical sciences · 2025Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant activation of the Hedgehog pathway drives tumorigenesis of many cancers, including glioblastoma. However, the sensitization mechanism of the G protein-coupled-like receptor smoothened (SMO), a key component of Hedgehog signaling, remains largely unknown.
resultsIn this study, we describe a novel protein SMO-193a.a. that is essential for Hedgehog signaling activation in glioblastoma. Encoded by circular SMO (circ-SMO), SMO-193a.a. is required for sonic hedgehog (Shh) induced SMO activation, via interacting with SMO, enhancing SMO cholesterol modification, and releasing SMO from the inhibition of patched transmembrane receptors. Deprivation of SMO-193a.a. in brain cancer stem cells attenuates Hedgehog signaling intensity and suppresses self-renewal, proliferation in vitro, and tumorigenicity in vivo. Moreover, circ-SMO/SMO-193a.a. is positively regulated by FUS, a direct transcriptional target of Gli1. Shh/Gli1/FUS/SMO-193a.a. form a positive feedback loop to sustain Hedgehog signaling activation in glioblastoma. Clinically, SMO-193a.a. is more specifically expressed in glioblastoma than SMO and is relevant to Gli1 expression. Higher expression of SMO-193a.a. predicts worse overall survival of glioblastoma patients, indicating its prognostic value.
conclusionsOur study reveals that SMO-193a.a., a novel protein encoded by circular SMO, is critical for Hedgehog signaling, drives glioblastoma tumorigenesis and is a novel target for glioblastoma treatment.
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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.