ArticleMolecular cancer2023
A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 77 citations in OpenAlex.
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- Metabolic remodeling by circular RNAs in gastric tumorigenesis: From mechanisms to biomarker discovery (Review).International journal of oncology · 2026Review
- The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.Medical oncology (Northwood, London, England) · 2026Review
- Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation.Journal of advanced research · 2026Review
- Circular RNA as emerging precision therapeutics: from RNA regulation to peptide translation.Precision clinical medicine · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- METTL7A inhibits progression of colorectal cancer through the SREBP1 / FDFT1 / SQLE / CYP51A1 / cholesterol metabolic pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- YTH N6-methyladenosine RNA binding protein 2 mediated mMolecular biomedicine · 2026Article
- Insights Into circRNA-Mediated Lipid Metabolism in Cancer Progression.Journal of cellular and molecular medicine · 2026Review
- Using Multi-Omics Methods to Understand Gouty Arthritis.Current rheumatology reviews · 2026Review
- Dysfunctional circular RNA network in major depressive disorder: dissecting the cell identity and potential clinical applications.Molecular psychiatry · 2026Review
- CircRNAs in hepatic lipid metabolism: regulatory mechanisms and clinical implications.Frontiers in genetics · 2026Review
- CircRAD23B-208aa Promotes Gastric Cancer Progression by Activating the Unfolded Protein Response through PDIA5 SUMOylation.Research (Washington, D.C.) · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Role of UGP2 as a Biomarker in Colorectal Cancer: Implications for Tumor Progression, Diagnosis, and Prognosis.Current issues in molecular biology · 2025Article
- Hypoxia-Induced Extracellular Vesicles and Non-Coding RNAs in Cancer: A Systematic Review of Tumor Dynamics and Therapeutic Implications in Preclinical Animal Models.Biomedicines · 2025Review
- A novel protein cPFKFB4 encoded by hsa_circ_0065394 strengthens PKM2-mediated glucose metabolic reprogramming to facilitate pancreatic cancer progression under hypoxia.Molecular cancer · 2025Article
- Recent advances of circular RNAs in gastrointestinal cancer.World journal of clinical oncology · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive.
methodsHypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC-MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses.
resultsA novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC.
conclusionscircINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.
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