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CTCF enhances pancreatic cancer progression via FLG-AS1-dependent epigenetic regulation and macrophage polarization

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资源类型：
Pubmed体系：
作者：
Liu Yihao[1,2,3] * ; Liu Pengyi[1,2,3] * ; Duan Songqi[4] * ; Lin Jiayu[1,2,3] * ; Qi Wenxin[5] ; Yu Zhengwei[2] ; Gao Xia[2] ; Sun Xiuqiao[2] ; Liu Jia[1,2,3] ; Lin Jiewei[1,2,3] ; Zhai Shuyu[1,2,3] ; Qin Kai[1,2,3] ; Cao Yizhi[1,2,3] ; Li Jingwei[1,2,3] ; Liu Yang[1,2,3] ; Chen Mengmin[1,2,3] ; Zou Siyi[1,2,3] ; Wen Chenlei[1,2,3] ; Wang Jiao[5] ; Fu Da[1,2,3] ; Wang Jiancheng[1,2,3] ; Bao Haili[1] ; Sun Keyan[1,2,3] ; Jiang Yu[1,2,3] ; Shen Baiyong[1,2,3] ;
机构： [1]Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. [2]Research Institute of Pancreatic Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China. [3]State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai 200025, China. [4]College of Food Science, Sichuan Agricultural University, Yaan, China. [5]School of Life Sciences, Shanghai University, Shanghai, China
出处：
DOI： 10.1038/s41418-024-01423-1
ISSN：

摘要：
CCCTC-binding factor (CTCF) regulates chromatin organization and is upregulated in pancreatic ductal adenocarcinoma (PDAC). We found that CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of EP300 and activation of the m6A reader IGF2BP2. This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. Moreover, FLG-AS1 directly interacts with HNRNPU to modulate alternative splicing of CSF1, thus promoting the M2 polarization of tumor associated macrophages (TAMs) in PDAC. The results indicated that CTCF-induced oncogenic modification of histone lactylation, m6A and alternative spilcing as multi-regulation modes of TAMs reprogramming in PDAC and identifies CTCF as a potential therapeutic target for PDAC immunotherapy whose inhibition M2 polarization through the IGF2BP2/CSF1/CSF1R axis. Curaxin combined with gemcitabine treatment has shown promising antitumor efficacy against PDAC.© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.

基金：
This work was sponsored by The National Natural Science Foundation of China (81871906 and 82073326), Basic Research Program of Shanghai (20JC1412200), the National Key Research and Development Program of China (2020YFA0113000) and PostGraduate Innovation Fund of Interdiscipline and New Medicine from School of Medicine of Shanghai University.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学 2 区 细胞生物学
第一作者：
第一作者机构： [1]Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. [2]Research Institute of Pancreatic Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China. [3]State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. [2]Research Institute of Pancreatic Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China. [3]State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
推荐引用方式(GB/T 7714)：
Liu Yihao,Liu Pengyi,Duan Songqi,et al.CTCF enhances pancreatic cancer progression via FLG-AS1-dependent epigenetic regulation and macrophage polarization[J].Cell Death And Differentiation.2024,doi:10.1038/s41418-024-01423-1.
APA：
Liu Yihao,Liu Pengyi,Duan Songqi,Lin Jiayu,Qi Wenxin...&Shen Baiyong.(2024).CTCF enhances pancreatic cancer progression via FLG-AS1-dependent epigenetic regulation and macrophage polarization.Cell Death And Differentiation,,
MLA：
Liu Yihao,et al."CTCF enhances pancreatic cancer progression via FLG-AS1-dependent epigenetic regulation and macrophage polarization".Cell Death And Differentiation .(2024)

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