ArticleDiagnostic pathology2020
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway.
Article in Diagnostic pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- The Transcriptional Role of Circular RNAs in Drug Resistance by Modulating the miRNA/mRNA Axis.Experientia supplementum (2012) · 2026Article
- Hepatocellular carcinoma drug resistance models.Cancer cell international · 2025Review
- Role of circular RNAs in cancer therapy resistance.Molecular cancer · 2025Review
- The role of circRNAs in resistance to doxorubicin.Cell communication and signaling : CCS · 2024Review
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- DEAD-Box Helicase 17 circRNA (circDDX17) Reduces Sorafenib Resistance and Tumorigenesis in Hepatocellular Carcinoma.Digestive diseases and sciences · 2024Article
- Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance.Cellular and molecular life sciences : CMLS · 2024Review
- Deciphering the impact of circRNA-mediated autophagy on tumor therapeutic resistance: a novel perspective.Cellular & molecular biology letters · 2024Review
- DNA damage response-related ncRNAs as regulators of therapy resistance in cancer.Frontiers in pharmacology · 2024Review
- Circ_0001944 Targets the miR-1292-5p/FBLN2 Axis to Facilitate Sorafenib Resistance in Hepatocellular Carcinoma by Impeding Ferroptosis.ImmunoTargets and therapy · 2024Article
- miRNAs as short non-coding RNAs in regulating doxorubicin resistance.Journal of cell communication and signaling · 2023Review
- The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- LncRNA model predicts liver cancer drug resistance and validateFrontiers in cell and developmental biology · 2023Article
- Noncoding RNA-mediated molecular bases of chemotherapy resistance in hepatocellular carcinoma.Cancer cell international · 2022Review
- Advances in the Study of CircRNAs in Tumor Drug Resistance.Frontiers in oncology · 2022Review
- Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- The functional roles, cross-talk and clinical implications of m6A modification and circRNA in hepatocellular carcinoma.International journal of biological sciences · 2021Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC).
methodsThe expression of circ_0003998 and microRNA (miR)-218-5p and eukaryotic translation initiation factor 5A-2 (EIF5A2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, migration and invasion were analyzed using cell counting kit-8, colony formation and transwell assay, respectively. The levels of matrix metallopeptidase 9 (MMP-9), E-cadherin, Vimentin, N-cadherin and EIF5A2 protein were detected using western blot. The interaction between miR-218-5p and circ_0003998 or EIF5A2 was confirmed by dual-luciferase reporter assay. In vivo experiments were performed using murine xenograft models.
resultsCirc_0003998 was elevated in HCC tissues, DOX-resistant tissues and cells, and circ_0003998 knockdown promoted DOX-sensitivity in HCC by inhibiting resistant cell viability, migration, invasion and EMT in vitro and enhanced DOX cytotoxicity in vivo. Bioinformatics analysis revealed circ_0003998 inhibited miR-218-5p expression, which was clarified to be a target of circ_0003998, and circ_0003998 knockdown sensitized HCC cell to DOX by sponging miR-218-5p. EIF5A2 was a target of miR-218-5p, and miR-218-5p mitigated DOX resistance in HCC cells through modulating EIF5A2 expression. Additionally, circ_0003998 served as a competing endogenous RNA for miR-218-5p to regulate EIF5A2 expression.
conclusionCirc_0003998 knockdown sensitized HCC cell to DOX by regulating miR-218-5p/EIF5A2 axis, indicating new markers of poor response to DOX and potential therapeutic strategies for the chemotherapy of HCC.
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