ArticleJournal of experimental & clinical cancer research : CR2020
A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 85 citations in OpenAlex.
- Histone Methylation: A Pivotal Epigenetic Driver of the Malignant Transformation of MASLD-HCC.Journal of hepatocellular carcinoma · 2026Review
- Treating human cancer by targeting EZH2.Genes & diseases · 2025Review
- The emerging functions and clinical implications of circRNAs in acute myeloid leukaemia.Cancer cell international · 2025Review
- Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases.Frontiers in oncology · 2025Review
- Diagnostic Accuracy of CircRNAs for Detecting Gastrointestinal Cancers: An Updated Meta-analysis.Medical journal of the Islamic Republic of Iran · 2025Article
- Interplay between JAK/STAT pathway and non-coding RNAs in different cancers.Non-coding RNA research · 2024Review
- CircDCAF8 promotes the progression of hepatocellular carcinoma through miR-217/NAP1L1 Axis, and induces angiogenesis and regorafenib resistance via exosome-mediated transfer.Journal of translational medicine · 2024Article
- CircSNX6 promotes proliferation, metastasis, and angiogenesis in hepatocellular carcinoma via miR-383-5p/VEGFA signaling pathway.Scientific reports · 2024Article
- The regulatory relationship between transcription factor STAT3 and noncoding RNA.Cellular & molecular biology letters · 2024Review
- Crosstalk Between circRNA and Tumor Microenvironment of Hepatocellular Carcinoma: Mechanism, Function and Applications.OncoTargets and therapy · 2024Review
- CRISPR/Cas9‑mediated EZH2 knockout suppresses the proliferation and migration of triple‑negative breast cancer cells.Oncology letters · 2023Article
- CircRNAs regulate the crosstalk between inflammation and tumorigenesis: The bilateral association and molecular mechanisms.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- EZH2 in hepatocellular carcinoma: progression, immunity, and potential targeting therapies.Experimental hematology & oncology · 2023Review
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Recent research progress of circular RNAs in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Circular RNAs in hepatocellular carcinoma: biogenesis, function, and pathology.Frontiers in genetics · 2023Review
- Behind the scenes: How RNA orchestrates the epigenetic regulation of gene expression.Frontiers in cell and developmental biology · 2023Review
- The expression pattern of pyroptosis-related genes predicts the prognosis and drug response of melanoma.Scientific reports · 2022Article
- CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex.Journal of experimental & clinical cancer research : CR · 2022Article
- circEXOC6B interacting with RRAGB, an mTORC1 activator, inhibits the progression of colorectal cancer by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop.Molecular cancer · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCircular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.
methodsqRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.
resultsCirc-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188-9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC.
conclusionsOur study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.
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