ArticleCancer cell international2021
Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- The involvement of circular RNAs in breast cancer metastasis: Insight into EMT-related signaling pathways.BioImpacts : BI · 2026Review
- PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.Clinical and experimental medicine · 2025Review
- MEOX1-mediated transcriptional regulation of circABHD3 exacerbates hepatic fibrosis through promoting m6A/YTHDF2-dependent YPEL3 mRNA decay to activate β-catenin signaling.PLoS genetics · 2025Article
- The Role of the Dysregulation of circRNAs Expression in Glioblastoma Multiforme.Journal of molecular neuroscience : MN · 2025Review
- The regulatory role of the circELMOD3-associated ceRNA network in the progression and prognosis of hepatocellular carcinoma.Frontiers in genetics · 2025Article
- Identification of Serum-Derived CricRNA Diagnostic Panel and Revealing Their Regulatory Mechanisms in HCV-HCC: A Cross-Sectional Study.Health science reports · 2024Article
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- WAVE3 Facilitates the Tumorigenesis and Metastasis of Tongue Squamous Cell Carcinoma via EMT.Applied biochemistry and biotechnology · 2024Article
- MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways.Cancer cell international · 2024Review
- Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks.Cell death & disease · 2024Review
- Bioinformatics-Based Construction of Immune-Related microRNA and mRNA Prognostic Models for Hepatocellular Carcinoma.Cancer management and research · 2024Article
- Crosstalk Between circRNA and Tumor Microenvironment of Hepatocellular Carcinoma: Mechanism, Function and Applications.OncoTargets and therapy · 2024Review
- Exosome Cargos as Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Differentially expressed non-coding RNAs and their regulatory networks in liver cancer.Heliyon · 2023Review
- Regulation of the tumor immune microenvironment by cancer-derived circular RNAs.Cell death & disease · 2023Review
- The current status and future of PD-L1 in liver cancer.Frontiers in immunology · 2023Review
- The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- Review of novel functions and implications of circular RNAs in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Recent research progress of circular RNAs in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEpithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness.
methodsHsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells.
resultsmiR-145 directly targeted the PD-L1 3'-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues.
conclusionOur findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.
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