ArticleBMC cancer2015
YY1 suppresses FEN1 over-expression and drug resistance in breast cancer.
Article in BMC cancer, 2015. 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, 65 citations in OpenAlex.
- The YYR (YY1- RKIP) Regulatory Axis in the pathogenesis of Cancer and Immune Evasion.Journal of experimental & clinical cancer research : CR · 2025Review
- A Validated Proteomic Signature of Basal-like Triple-Negative Breast Cancer Subtypes Obtained from Publicly Available Data.Cancers · 2025Article
- Yin Yang 1 (YY1) as a Central Node in Drug Resistance Pathways: Potential for Combination Strategies in Cancer Therapy.Biomolecules · 2025Review
- Molecular Mechanisms of Radiation Resistance in Breast Cancer: A Systematic Review of Radiosensitization Strategies.Current issues in molecular biology · 2025Review
- The endonuclease FEN1 mediates activation of STAT3 and facilitates proliferation and metastasis in breast cancer.Molecular biology reports · 2024Article
- FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.International journal of molecular sciences · 2024Article
- Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1.Bioscience reports · 2023Article
- Reconstruction of the regulatory hypermethylation network controlling hepatocellular carcinoma development during hepatitis C viral infection.Journal of integrative bioinformatics · 2023Article
- Dysregulation of alternative splicing contributes to multiple myeloma pathogenesis.British journal of cancer · 2023Article
- INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer.Frontiers in cell and developmental biology · 2023Article
- Dissecting the roles and clinical potential of YY1 in the tumor microenvironment.Frontiers in oncology · 2023Review
- Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer.International journal of molecular sciences · 2022Review
- Lung cancer: progression of heat shock protein 70 in association with flap endonuclease 1 protein.3 Biotech · 2021Article
- FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis.Annals of translational medicine · 2021Article
- Roles of the Immune/Methylation/Autophagy Landscape on Single-Cell Genotypes and Stroke Risk in Breast Cancer Microenvironment.Oxidative medicine and cellular longevity · 2021Article
- The Clinical Significance of the Expression of FEN1 in Primary Osteosarcoma.International journal of general medicine · 2021Article
- Article
- CircRNA circYY1 (hsa_circ_0101187) Modulates Cell Glycolysis and Malignancy Through Regulating YY1 Expression by Sponging miR-769-3p in Breast Cancer.Cancer management and research · 2021Article
- Biological and clinical significance of flap endonuclease‑1 in triple‑negative breast cancer: Support of metastasis and a poor prognosis.Oncology reports · 2020Article
- Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDrug resistance is a major challenge in cancer therapeutics. Abundant evidence indicates that DNA repair systems are enhanced after repetitive chemotherapeutic treatments, rendering cancers cells drug-resistant. Flap endonuclease 1 (FEN1) plays critical roles in DNA replication and repair and in counteracting replication stress, which is a key mechanism for many chemotherapeutic drugs to kill cancer cells. FEN1 was previously shown to be upregulated in response to DNA damaging agents. However, it is unclear about the transcription factors that regulate FEN1 expression in human cancer. More importantly, it is unknown whether up-regulation of FEN1 has an adverse impact on the prognosis of chemotherapeutic treatments of human cancers.
methodsTo reveal regulation mechanism of FEN1 expression, we search and identify FEN1 transcription factors or repressors and investigate their function on FEN1 expression by using a combination of biochemical, molecular, and cellular approaches. Furthermore, to gain insights into the impact of FEN1 levels on the response of human cancer to therapeutic treatments, we determine FEN1 levels in human breast cancer specimens and correlate them to the response to treatments and the survivorship of corresponding breast cancer patients.
resultsWe observe that FEN1 is significantly up-regulated upon treatment of chemotherapeutic drugs such as mitomycin C (MMC) and Taxol in breast cancer cells. We identify that the transcription factor/repressor YY1 binds to the FEN1 promoter and suppresses the expression of FEN1 gene. In response to the drug treatments, YY1 is dissociated from the FEN1 promoter region leading over-expression of FEN1. Overexpression of YY1 in the cells results in down-regulation of FEN1 and sensitization of the cancer cells to MMC or taxol. Furthermore, we observe that the level of FEN1 is inversely correlated with cancer drug and radiation resistance and with survivorship in breast cancer patients.
conclusionAltogether, our current data indicate that YY1 is a transcription repressor of FEN1 regulating FEN1 levels in response to DNA damaging agents. FEN1 is up-regulated in human breast cancer and its levels inversely correlated with cancer drug and radiation resistance and with survivorship in breast cancer patients.
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