ArticleJournal of experimental & clinical cancer research : CR2023
Energy stress-induced circZFR enhances oxidative phosphorylation in lung adenocarcinoma via regulating alternative splicing.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- circZNF148 Drives Glucose Metabolism Reprogramming to Enhance Metastasis and Immune Evasion via HK1 Stabilization in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CircSPARC promotes esophageal squamous cell carcinoma through an HNRNPC-EPN2 splicing axis that activates Wnt/β-Catenin signaling.Molecular cancer · 2026Article
- MYO1B in human disease: an actin-based motor linking membrane trafficking to oncogenic signaling, metastasis, and vascular aging.Frontiers in oncology · 2026Review
- Identification and validation of core oxidative phosphorylation-related genes as biomarkers for immune response and diagnosis in burn injury.Frontiers in immunology · 2026Article
- Circular RNAs: Key Regulators of Tumor Metabolic Reprogramming and Clinical Translation.Oncology research · 2026Review
- Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications.Research (Washington, D.C.) · 2026Review
- Silencing of circRERE(4-5) inhibits ONECUT2-mediated tumorigenesis and metastasis in gastric cancer.Frontiers in immunology · 2026Article
- The crosstalk between non-coding RNAs and oxidative stress in cancer progression.Genes & diseases · 2025Review
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- [High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is associated with poor patient prognosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- CircZFR functions in cancer from molecular networks to precision therapy.Frontiers in genetics · 2025Review
- Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities.MedComm · 2024Review
- The crosstalk between alternative splicing and circular RNA in cancer: pathogenic insights and therapeutic implications.Cellular & molecular biology letters · 2024Review
- Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma.Journal of thoracic disease · 2024Article
- Roles and mechanisms of circular RNA in respiratory system cancers.Frontiers in oncology · 2024Review
- Correction: Energy stress-induced circZFR enhances oxidative phosphorylation in lung adenocarcinoma via regulating alternative splicing.Journal of experimental & clinical cancer research : CR · 2023Article
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCircular RNAs (circRNAs) contribute to multiple biological functions and are also involved in pathological conditions such as cancer. However, the role of circRNAs in metabolic reprogramming, especially upon energy stress in lung adenocarcinoma (LUAD), remains largely unknown.
methodsEnergy stress-induced circRNA was screened by circRNA profiling and glucose deprivation assays. RNA-seq, real-time cell analyzer system (RTCA) and measurement of oxygen consumption rate (OCR) were performed to explore the biological functions of circZFR in LUAD. The underlying mechanisms were investigated using circRNA pull-down, RNA immunoprecipitation, immunoprecipitation and bioinformatics analysis of alternative splicing. Clinical implications of circZFR were assessed in 92 pairs of LUAD tissues and adjacent non-tumor tissues, validated in established patient-derived tumor xenograft (PDTX) model.
resultsCircZFR is induced by glucose deprivation and is significantly upregulated in LUAD compared to adjacent non-tumor tissues, enhancing oxidative phosphorylation (OXPHOS) for adaptation to energy stress. CircZFR is strongly associated with higher T stage and poor prognosis in patients with LUAD. Mechanistically, circZFR protects heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) from degradation by ubiquitination to regulate alternative splicing, such as myosin IB (MYO1B), and subsequently activates the AKT-mTOR pathway to facilitate OXPHOS.
conclusionOur study provides new insights into the role of circRNAs in anticancer metabolic therapies and expands our understanding of alternative splicing.
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