ArticleJournal of experimental & clinical cancer research : CR2024
N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 21 citations in OpenAlex.
- Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).International journal of molecular medicine · 2026Review
- WTAP-Mediated m6A Modification of TXNDC5 mRNA Promotes Cervical Carcinogenesis.The Kaohsiung journal of medical sciences · 2026Article
- N6-methyladenosine (m6A)-circHECA facilitates the differentiation of SHF stem cells into hair follicle lineage through miR-449a-5p/LEF1 mediated Wnt/β-catenin pathway in cashmere goats.Animal bioscience · 2026Article
- Novel Insights into the Role of circRNAs in Cancer Immunotherapy Resistance and Clinical Implications.International journal of molecular sciences · 2026Review
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Advances in Multi-Omics Research on Biomarkers of Intrahepatic Cholangiocarcinoma.Current issues in molecular biology · 2025Review
- m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review).International journal of molecular medicine · 2025Review
- The diverse roles of circular RNAs in cholangiocarcinoma.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Transcriptome sequencing showed the differential expression of circRNAs in human pulmonary microvascular endothelial cells in acute respiratory distress syndrome.Journal of thoracic disease · 2025Article
- The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness.Biomedicines · 2025Review
- Circular RNAs: key players in tumor immune evasion.Molecular and cellular biochemistry · 2025Review
- A lipid metabolism related gene signature predicts postoperative recurrence in pancreatic cancer through multicenter cohort validation.Scientific reports · 2025Article
- Circ_RUSC2 Sequesters miR-661 and Elevates TUSC2 Expression to Suppress Colorectal Cancer Progression.International journal of molecular sciences · 2025Article
- The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes.Cell & bioscience · 2025Review
- Review
- The role of N(6)-methyladenosine (m6a) modification in cancer: recent advances and future directions.EXCLI journal · 2025Review
- Circular RNAs and Cancers.Advances in experimental medicine and biology · 2025Review
- m6A-modified circXPO1 accelerates colorectal cancer progression via interaction with FMRP to promote WWC2 mRNA decay.Journal of translational medicine · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRefractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC.
methodsCircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs.
resultsHerein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients.
conclusionsTaken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.
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