ArticleRedox biology2018
Prolonged oxidative stress down-regulates Early B cell factor 1 with inhibition of its tumor suppressive function against cholangiocarcinoma genesis.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 80 citations in OpenAlex.
- EBF1 Regulates Cardiac Development Through Fibroblast to Myocyte Signaling.Journal of cardiovascular development and disease · 2026Article
- Forsythiaside A inhibits the progression of intrahepatic cholangiocarcinoma partially via suppressing oxidative stress-induced hepatic stellate cell activation and macrophage polarization.BMC biotechnology · 2026Article
- Prolonged Oxidative Stress Drives p53/p21-Mediated Senescence and Degenerative Adaptation in Kidney-Derived Cells.Oxidative medicine and cellular longevity · 2026Article
- Advances in Research on the B-Lineage Transcription Factor EBF1 in Solid Tumors.International journal of molecular sciences · 2025Review
- Inhibition of the FEN1-PBX1 axis elicits cellular senescence in breast cancer via the increased intracellular reactive oxygen species levels.Journal of translational medicine · 2025Article
- Identification of the EBF1/ETS2/KLF2-miR-126-Gene Feed-Forward Loop in Breast Carcinogenesis and Stemness.International journal of molecular sciences · 2025Article
- Antioxidative and anticancer effects of Tacca chantrieri extract enhancing cisplatin sensitivity in cholangiocarcinoma cells.PloS one · 2025Article
- Anti-CD24 Antibody Plus Liposomal Doxorubicin for the Management of Residual Cancers After Incomplete Radiofrequency Ablation.ImmunoTargets and therapy · 2025Article
- Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities.PLoS neglected tropical diseases · 2024Article
- Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.Cancer management and research · 2024Review
- Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma.Antioxidants (Basel, Switzerland) · 2023Review
- Overexpression of Insulin Receptor Substrate 1 (IRS1) Relates to Poor Prognosis and Promotes Proliferation, Stemness, Migration, and Oxidative Stress Resistance in Cholangiocarcinoma.International journal of molecular sciences · 2023Article
- LncRNA-mRNA expression profile and functional network of vascular dysfunction in septic rats.European journal of medical research · 2023Article
- EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas.Frontiers in immunology · 2023Article
- Bioinformatics Analysis IdentifiesDisease markers · 2023Article
- Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves ofNutrients · 2022Article
- Tumor Microenvironment and its Implications for Antitumor Immunity in Cholangiocarcinoma: Future Perspectives for Novel Therapies.International journal of biological sciences · 2022Review
- Long noncoding RNA IL6-AS1 is highly expressed in chronic obstructive pulmonary disease and is associated with interleukin 6 by targeting miR-149-5p and early B-cell factor 1.Clinical and translational medicine · 2021Article
- Investigation of the hepatic development in the coculture of hiPSCs-derived LSECs and HLCs in a fluidic microenvironment.APL bioengineering · 2021Article
- Promoter hypermethylation of early B cell factor 1 (EBF1) is associated with cholangiocarcinoma progression.Journal of Cancer · 2021Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early B cell factor 1 (EBF1) is a transcription factor involved in the differentiation of several stem cell lineages and it is a negative regulator of estrogen receptors. EBF1 is down-regulated in many tumors, and is believed to play suppressive roles in cancer promotion and progression. However, the functional roles of EBF1 in carcinogenesis are unclear. Liver fluke-infection-associated cholangiocarcinoma (CCA) is an oxidative stress-driven cancer of bile duct epithelium. In this study, we investigated EBF1 expression in tissues from CCA patients, CCA cell lines (KKU-213, KKU-214 and KKU-156), cholangiocyte (MMNK1) and its oxidative stress-resistant (ox-MMNK1-L) cell lines. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was used as an oxidative stress marker. Our results revealed that EBF1 expression was suppressed in cancer cells compared with the individual normal bile duct cells at tumor adjacent areas of CCA tissues. CCA patients with low EBF1 expression and high formation of 8-oxodG were shown to correlate with poor survival. Moreover, EBF1 was suppressed in the oxidative stress-resistant cell line and all of CCA cell lines compared to the cholangiocyte cell line. This suggests that prolonged oxidative stress suppressed EBF1 expression and the reduced EBF1 level may facilitate CCA genesis. To elucidate the significance of EBF1 suppression in CCA genesis, EBF1 expression of the MMNK1 cell line was down-regulated by siRNA technique, and its effects on stem cell properties (CD133 and Oct3/4 expressions), tumorigenic properties (cell proliferation, wound healing and cell migration), estrogen responsive gene (TFF1), estrogen-stimulated wound healing, and cell migration were examined. The results showed that CD133, Oct3/4 and TFF1 expression levels, wound healing, and cell migration of EBF1 knockdown-MMNK1 cells were significantly increased. Also, cell migration of EBF1-knockdown cells was significantly enhanced after 17β-estradiol treatment. Our findings suggest that EBF1 down-regulation via oxidative stress induces stem cell properties, tumorigenic properties and estrogen responses of cholangiocytes leading to CCA genesis with aggressive clinical outcomes.
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