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FOXK1 promotes hormonally responsive breast carcinogenesis by suppressing apoptosis

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机构: [1]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. [2]Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [3]Beijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, China. [4]National Human Diseases Animal Model Resource Center, The Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &amp [5]Peking Union Medical College, Beijing, China. [5]NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing, China. [6]Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing, China.
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关键词: apoptosis estrogen receptor-positive breast cancer FOXK1 transcription repression

摘要:
Globally, breast cancer constitutes the predominant malignancy in women. Abnormal regulation of epigenetic factors plays a key role in the development of tumors. Anti-apoptosis is a characteristic of tumor cells. Therefore, exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive (ER+ ) breast cancer. We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions. ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites. To validate the ChIP-seq results, qChIP, western blotting, and quantitative polymerase chain reaction (qPCR) were performed. Through TUNEL assay, cell counting assay, colony formation assay, and the mouse xenograft models, the effect of FOXK1 on breast cancer progression was detected. Finally, by analyzing online databases, the correlation between FOXK1 and the survival of breast cancer patients was examined.FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway. Abnormally high expression of FOXK1 prevents the apoptosis of ER+ breast cancer cells in vitro and promotes ER+ breast tumor progression in vivo. Furthermore, the expression of FOXK1 is negatively correlated with the survival of ER+ breast cancer patients.FOXK1 promotes ER+ breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+ breast cancer treatment.© 2024 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 生化与分子生物学 3 区 医学:研究与实验
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 生化与分子生物学 3 区 医学:研究与实验
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Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
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通讯机构: [1]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. [2]Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [3]Beijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, China. [4]National Human Diseases Animal Model Resource Center, The Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &amp [5]Peking Union Medical College, Beijing, China. [5]NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing, China. [6]Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing, China. [*1]Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China [*2]National Human Diseases Animal Model Resource Center, The Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China. [*3]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
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