ArticleCancers2021
MiR-125b-5p Is Involved in Sorafenib Resistance through Ataxin-1-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Extracellular matrix-growth factor signalling drives the oncogenic mir-125b-2/UCK2 axis in hepatocellular carcinoma.Hereditas · 2026Article
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- Prognostic Role of Circulating miR-141 in Early Diagnosis of Colorectal Cancer.Medicina (Kaunas, Lithuania) · 2025Article
- Revisiting Treatment Strategies: Addressing Epithelial-to-Mesenchymal Transition-Induced Resistance in Hepatocellular Carcinoma.BME frontiers · 2025Review
- Exosomal miR-199a-3p Secreted From Cancer-Associated Adipocytes Promotes Pancreatic Cancer Progression.Cancer medicine · 2024Article
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- MicroRNAs in Hepatocellular Carcinoma: Insights into Regulatory Mechanisms, Clinical Significance, and Therapeutic Potential.Cancer management and research · 2024Review
- Resveratrol restrains colorectal cancer metastasis by regulating miR-125b-5p/TRAF6 signaling axis.American journal of cancer research · 2024Article
- Circ-SNX27 sponging miR-375/RPN1 axis contributes to hepatocellular carcinoma progression.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches.Pharmaceutics · 2023Review
- The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- Construction and validation of prognostic signature for hepatocellular carcinoma basing on hepatitis B virus related specific genes.Infectious agents and cancer · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment.Cancer cell international · 2022Review
- Review
- CHRNA5 Contributes to Hepatocellular Carcinoma Progression by Regulating YAP Activity.Pharmaceutics · 2022Article
- Flavonoids Inhibit Cancer by Regulating the Competing Endogenous RNA Network.Frontiers in oncology · 2022Review
- Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications.Frontiers in oncology · 2022Review
- MicroRNA-1205 Suppresses Hepatocellular Carcinoma Cell Proliferation via a CSNK2B/CDK4 Axis.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism of resistance to sorafenib in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the miRNAs responsible for resistance. Drug sensitivity, migration/invasion capabilities, and epithelial-mesenchymal transition (EMT) properties were analyzed by biochemical methods. The clinical relevance of the target genes to survival in HCC patients were assessed using a public database. Four miRNAs were significantly upregulated in PLC/PRF5-R1/-R2 compared with PLC/PRF5. Among them, miR-125b-5p mimic-transfected PLC/PRF5 cells (PLC/PRF5-miR125b) and showed a significantly higher IC50 for sorafenib compared with controls, while the other miRNA mimics did not. PLC/PRF5-miR125b showed lower E-cadherin and higher Snail and vimentin expression-findings similar to those for PLC/PRF5-R2-which suggests the induction of EMT in those cells. PLC/PRF5-miR125b exhibited significantly higher migration and invasion capabilities and induced sorafenib resistance in an in vivo mouse model. Bioinformatic analysis revealed ataxin-1 as a target gene of miR-125b-5p. PLC/PRF5 cells transfected with ataxin-1 siRNA showed a significantly higher IC50, higher migration/invasion capability, higher cancer stem cell population, and an EMT phenotype. Median overall survival in the low-ataxin-1 patient group was significantly shorter than in the high-ataxin-1 group. In conclusion, miR-125b-5p suppressed ataxin-1 and consequently induced Snail-mediated EMT and stemness, leading to a poor prognosis in HCC patients.
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Registered trials
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