ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- NAT10/acProceedings of the National Academy of Sciences of the United States of America · 2026Article
- The allosteric IDH1 inhibitor ivosidenib overcomes chemoresistance in intrahepatic cholangiocarcinoma models expressing wild-type IDH1.The Journal of clinical investigation · 2026Article
- Circular RNAs: Key Regulators of Tumor Metabolic Reprogramming and Clinical Translation.Oncology research · 2026Review
- Recent advances in research on the multifactorial mechanisms underlying paclitaxel resistance and translational intervention strategies.Frontiers in pharmacology · 2026Review
- Dual-functional nanovesicles simultaneously inhibit stromal fibrosis and angiogenesis to suppress cholangiocarcinoma progression.Journal of nanobiotechnology · 2025Article
- Integrative analysis of scRNA-seq and RNA-seq to investigate the prognostic value of lactylation and fibroblast-related genes in intrahepatic cholangiocarcinoma.Scientific reports · 2025Article
- The functions of circular RNAs and long noncoding RNAs in cholangiocarcinoma.Discover oncology · 2025Review
- Targeting SERPINB3-MAPK axis-mediated cuproptosis resistance enhances the response to antitumor immunotherapy.Molecular cancer · 2025Article
- Advances in Multi-Omics Research on Biomarkers of Intrahepatic Cholangiocarcinoma.Current issues in molecular biology · 2025Review
- The diverse roles of circular RNAs in cholangiocarcinoma.Medical oncology (Northwood, London, England) · 2025Review
- Circular RNAs: key regulators of paclitaxel sensitivity and resistance in cancer.European journal of medical research · 2025Review
- [Research progress in the role of STMN1 in tumor].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanisms and therapeutic implications of gene expression regulation by circRNA-protein interactions in cancer.Communications biology · 2025Review
- Article
- The Emerging Role of IGF2BP2 in Cancer Therapy Resistance: From Molecular Mechanism to Future Potential.International journal of molecular sciences · 2024Review
- cNEK6 induces gemcitabine resistance by promoting glycolysis in pancreatic ductal adenocarcinoma via the SNRPA/PPA2c/mTORC1 axis.Cell death & disease · 2024Article
- CircUGP2 Suppresses Intrahepatic Cholangiocarcinoma Progression via p53 Signaling Through Interacting With PURB to Regulate ADGRB1 Transcription and Sponging miR-3191-5p.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.Journal of translational medicine · 2024Article
- Long Non-coding RNA DNM3OS: Pathogenic Roles and Molecular Mechanisms in Pathophysiological Processes.Current medicinal chemistry · 2024Review
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Intrahepatic cholangiocarcinoma (ICC) is characterized by its dense fibrotic microenvironment and highly malignant nature, which are associated with chemotherapy resistance and very poor prognosis. Although circRNAs have emerged as important regulators in cancer biology, their role in ICC remains largely unclear. Herein, a circular RNA, cPKM is identified, which is upregulated in ICC and associated with poor prognosis. Silencing cPKM in ICC cells reduces TGFB1 release and stromal fibrosis, inhibits STMN1 expression, and suppresses ICC growth and metastasis, moreover, it also leads to overcoming paclitaxel resistance. This is regulated by the interactions of cPKM with miR-199a-5p or IGF2BP2 and by the ability of cPKM to stabilize STMN1/TGFB1 mRNA. Based on these findings, a Trojan horse nanotherapy strategy with co-loading of siRNA against cPKM (si-cPKM) and paclitaxel (PTX) is developed. The siRNA/PTX co-loaded nanosystem (Trojan horse) efficiently penetrates tumor tissues, releases si-cPKM and paclitaxel (soldiers), promotes paclitaxel sensitization, and suppresses ICC proliferation and metastasis in vivo. Furthermore, it alleviates the fibrosis of ICC tumor stroma and reopens collapsed tumor vessels (opening the gates), thus enhancing the efficacy of the standard chemotherapy regimen (main force). This novel nanotherapy provides a promising new strategy for ICC treatment.
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