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H19 promotes polarization and alternative splicing in tumor-associated macrophages, facilitating pancreatic cancer progression

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收录情况： ◇ SCIE

作者：
Liu Pengyi[1,2,3] * ; Gao Xia[4] * ; Yu Zhengwei[5] * ; Liu Yang[1,2,3] ; Liu Yihao[1,2,3] ; Lin Jiayu[1,2,3] ; Cao Yizhi[1,2,3] ; Zhai Shuyu[1,2,3] ; Li Jingwei[1,2,3] ; Huang Yishu[1,2,3] ; Zou Siyi[1,2,3] ; Wen Chenlei[1,2,3] ; Fu Da[1,2,3] ; Lin Jiewei[6] ; Shen Baiyong[1,2,3] ;
机构： [1]Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China [2]Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China [3]State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China [4]Department of Pathology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [5]Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China [6]Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
出处：
DOI： 10.1016/j.canlet.2024.217389
ISSN：

关键词： Tumor-associated macrophages H19 Pancreatic cancer Alternative splicing Ruxolitinib

摘要：
Tumor-associated macrophages (TAMs) play a crucial physiological role in the pancreatic tumor microenvironment. However, the role of long non-coding RNAs (lncRNAs) in TAMs within pancreatic tumors remains unclear. By lncRNA sequencing between TAMs and resident macrophages from normal tissues in pancreatic cancer, it is found that H19 is highly expressed in TAMs and is correlated with the prognosis and stages of pancreatic cancer. Constructing a co-culture model of THP-1 derived TAMs and pancreatic cancer cells, H19 promotes the polarization of TAMs towards the M2 phenotype and the secretion of IL-6, IL-10, and TGF-β, both in vivo and in vitro, indirectly enhancing pancreatic cancer proliferation and metastasis. Mechanistically, H19 competitively binds to the mRNA of YTHDC1 with MiR-107, and also interacts with the YTHDC1 protein, regulating the stability of SRSF1 and thereby affecting the alternative splicing of IL-6 and IL-10. Utilizing organoids and the patient-derived xenograft (PDX) model, it is found that ruxolitinib may represent a promising treatment option for PDAC patients with high H19 expression.Copyright © 2024 Elsevier B.V. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China [grant numbers 82273356, 82073326] and National Nature Science Foundation of China [grant number 82303294]
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外文
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出版当年[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
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出版当年[2023]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China [2]Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China [3]State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong 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, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China [2]Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China [3]State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
推荐引用方式(GB/T 7714)：
Liu Pengyi,Gao Xia,Yu Zhengwei,et al.H19 promotes polarization and alternative splicing in tumor-associated macrophages, facilitating pancreatic cancer progression[J].Cancer Letters.2025,611:217389.doi:10.1016/j.canlet.2024.217389.
APA：
Liu Pengyi,Gao Xia,Yu Zhengwei,Liu Yang,Liu Yihao...&Shen Baiyong.(2025).H19 promotes polarization and alternative splicing in tumor-associated macrophages, facilitating pancreatic cancer progression.Cancer Letters,611,
MLA：
Liu Pengyi,et al."H19 promotes polarization and alternative splicing in tumor-associated macrophages, facilitating pancreatic cancer progression".Cancer Letters 611.(2025):217389

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