ArticleJournal of experimental & clinical cancer research : CR2023
CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma.
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 27 papers.
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Who cites it
27 citing papers in PubMed, 30 citations in OpenAlex.
- OTUD6A-Mediated Deubiquitination of PRDX1 Protects Against Oral Ulcer by Restoring Mitochondrial Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated GWAS and eQTL Colocalization Identified Candidate Genes for Growth Traits in Pigs.Biology · 2026Article
- Patient-Derived 3D-Bioprinted Intrahepatic Cholangiocarcinoma Models Recapitulate Tumor Autologous Traits and Predict Personalized Adjuvant Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Non-coding RNAs: modulators of signaling pathways and prognostic biomarkers in digestive system cancer.Molecular cancer · 2026Review
- The functions of circular RNAs and long noncoding RNAs in cholangiocarcinoma.Discover oncology · 2025Review
- KAL suppresses cholangiocarcinoma growth via downregulating miR-21 and modulating the PTEN/AKT signaling pathway.Scientific reports · 2025Article
- Advances in Multi-Omics Research on Biomarkers of Intrahepatic Cholangiocarcinoma.Current issues in molecular biology · 2025Review
- Review: Progress of the NLRP3 inflammasome in tumours and perspectives for cholangiocarcinoma.Cell communication and signaling : CCS · 2025Review
- The diverse roles of circular RNAs in cholangiocarcinoma.Medical oncology (Northwood, London, England) · 2025Review
- The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness.Biomedicines · 2025Review
- OTUD1 inhibits osteoclast differentiation and osteoclastic bone loss through deubiquitinating and stabilizing PRDX1.Theranostics · 2025Article
- Circular RNAs and Cancers.Advances in experimental medicine and biology · 2025Review
- Epigenetic Impact of Curcumin and Thymoquinone on Cancer Therapeutics.Current medicinal chemistry · 2025Review
- Genetic Uncertainties Fueling Cholangiocarcinoma Progression.Current genomics · 2025Review
- circWWC3 enhances the progression of triple-negative breast cancer by interacting with vimentin to regulate the secretion of CSF2.Frontiers in immunology · 2025Article
- Crosstalk between RNA-binding proteins and non-coding RNAs in tumors: molecular mechanisms, and clinical significance.International journal of biological sciences · 2025Review
- Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities.MedComm · 2024Review
- Unveil Intrahepatic Cholangiocarcinoma Heterogeneity through the Lens of Omics and Multi-Omics Approaches.Cancers · 2024Review
- Induction of Peroxiredoxin 1 by Hypoxia Promotes Cellular Autophagy and Cell Proliferation in Oral Leukoplakia via HIF-1α/BNIP3 Pathway.Journal of molecular histology · 2024Article
- Biological functions of circRNA in regulating the hallmarks of gastrointestinal cancer (Review).International journal of oncology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIncreasing evidence shows that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a crucial role in the development of cancers, including intrahepatic cholangiocarcinoma (iCCA). Nevertheless, their functions and exact mechanisms in iCCA progression and metastasis are still unclear. Ipatasertib is a highly selective inhibitor of AKT that inhibits tumor growth by blocking the PI3K/AKT pathway. In addition, phosphatase and tensin homolog (PTEN) can also inhibit the activation of the PI3K/AKT pathway, but it is not clear whether the cZNF215-PRDX-PTEN axis plays a role in the antitumor activity of ipatasertib.
methodsWe identified a new circRNA (circZNF215, termed cZNF215) through high-throughput circRNA sequencing (circRNA-seq). In addition, RT‒qPCR, immunoblot assay, RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and fluorescence in situ hybridization assay (FISH) were used to investigate the interaction of cZNF215 with peroxiredoxin 1 (PRDX1). Coimmunoprecipitation (Co-IP) assays and duolink in situ proximity ligation assays (PLAs) were conducted to analyze the effects of cZNF215 on the interaction between PRDX1 and PTEN. Finally, we tested the potential effects of cZNF215 on the antitumor activity of ipatasertib with in vivo experiments.
resultsWe found that cZNF215 expression was obviously upregulated in iCCA tissues with postoperative metastases and was correlated with iCCA metastasis and poor outcome in patients with iCCA. We further revealed that overexpression of cZNF215 promoted iCCA cell growth and metastasis in vitro and in vivo, while cZNF215 knockdown had the opposite effect. Mechanistic studies suggested that cZNF215 competitively interacted with PRDX1, which blocked the association between PRDX1 and PTEN, subsequently leading to oxidation-induced inactivation of the PTEN/AKT pathway and finally contributing to iCCA progression and metastasis. Additionally, we also revealed that silencing cZNF215 in iCCA cells had the potential to enhance the antitumor effect of ipatasertib.
conclusionsOur study demonstrates that cZNF215 facilitates iCCA progression and metastasis by regulating the PTEN/AKT pathway and may serve as a novel prognostic predictor in patients with iCCA.
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