更新于：2024-11-01

PDAP1

更新于：2024-11-01

基本信息

别名

28 kDa heat- and acid-stable phosphoprotein、HASPP28、PAP

+ [5]

简介

Enhances PDGFA-stimulated cell growth in fibroblasts, but inhibits the mitogenic effect of PDGFB.

关联

项与 PDAP1 相关的药物

CN114195903

专利挖掘

靶点

PDAP1

作用机制-

在研机构

第四军医大学

原研机构

第四军医大学

在研适应症

胃肠道疾病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PDAP1 相关的临床结果

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100 项与 PDAP1 相关的转化医学

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0 项与 PDAP1 相关的专利（医药）

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项与 PDAP1 相关的文献（医药）

2024-04-01·Immunity, Inflammation and Disease

Analysis of network expression and immune infiltration of disulfidptosis‐related genes in chronic obstructive pulmonary disease

Article

作者: You, Zhangqiang ; Cheng, Yan ; Zhu, Tao ; Zeng, Qiang ; Dai, Guangming ; Liu, Yanqun ; Wang, Juan

AbstractBackgroundChronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis‐related genes (DRGs) in COPD remain unclear.MethodsThe expression of DRGs was identified by analyzing RNA sequencing (RNA‐seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co‐expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes.ResultsWe identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke‐induced COPD mouse lung tissues and bronchial epithelial cells (BEAS‐2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate.ConclusionWe highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

2022-11-01·Cancer Science

Pancreatic ductal adenocarcinoma cells regulated the gemcitabine‐resistance function of CAFs by LINC00460

Article

作者: Zhao, Wei ; Ni, Xuhao ; Yin, Xiao‐Yu ; Hou, Xun ; Wu, Xiao ; Li, Jian‐Hui ; Li, Ya‐Xiong ; Li, Shi‐Jin ; Zhu, Xiao‐Xu

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC‐PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull‐down, LC–MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine‐resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC‐PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460.

2022-08-01·Cancer Communications

PDGFA‐associated protein 1 is a novel target of c‐Myc and contributes to colorectal cancer initiation and progression

Article

作者: Tian, Ruo‐Fei ; Chen, Zhi‐Nan ; Li, Ling ; Wang, Shi‐Jie ; Fu, Xin ; Yang, Ting ; Chen, Xi ; Wei, Wei ; Li, Hong‐Wei ; Qian, Mei‐Rui ; Wang, Bin ; Dou, Jian‐Hua ; Nan, Gang ; Cui, Hong‐Yong ; Sun, Xiu‐Xuan ; Zhu, Yu‐Meng ; Lin, Peng ; Jiang, Jian‐Li

AbstractBackgroundThe mechanism underlying colorectal cancer (CRC) initiation and progression remains elusive, and overall survival is far from satisfactory. Previous studies have shown that PDGFA‐associated protein 1 (PDAP1) is upregulated in several cancers including CRC. Here, we aimed to identify the cause and consequence of PDAP1 dysregulation in CRC and evaluate its role as a potential therapeutic target.MethodsMulti‐omics data analysis was performed to identify potential key players in CRC initiation and progression. Immunohistochemistry (IHC) staining was applied to determine the expression pattern of PDAP1 in CRC tissues. Pdap1 conditional knockout mice were used to establish colitis and CRC mouse models. RNA sequencing, a phosphoprotein antibody array, western blotting, histological analysis, 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation assay, and interactome analysis were applied to identify the underlying mechanisms of PDAP1. A human patient‐derived xenograft (PDX) model was used to assess the potential of PDAP1 as a therapeutic target.ResultsPDAP1 was identified as a potential key player in CRC development using multi‐omics data analysis. PDAP1 was overexpressed in CRC cells and correlated with reduced overall survival. Further investigation showed that PDAP1 was critical for the regulation of cell proliferation, migration, invasion, and metastasis. Significantly, depletion of Pdap1 in intestinal epithelial cells impaired mucosal restitution in dextran sulfate sodium salt‐induced colitis and inhibited tumor initiation and growth in colitis‐associated cancers. Mechanistic studies showed that c‐Myc directly transactivated PDAP1, which contributed to the high PDAP1 expression in CRC cells. PDAP1 interacted with the juxtamembrane domain of epidermal growth factor receptor (EGFR) and facilitated EGFR‐mitogen‐activated protein kinase (MAPK) signaling activation, which resulted in FOS‐related antigen 1 (FRA‐1) expression, thereby facilitating CRC progression. Notably, silencing of PDAP1 could hinder the growth of patient‐derived xenografts that sustain high PDAP1 levels.ConclusionsPDAP1 facilitates mucosal restitution and carcinogenesis in colitis‐associated cancer. c‐Myc‐driven upregulation of PDAP1 promotes proliferation, migration, invasion, and metastasis of CRC cells via the EGFR‐MAPK‐FRA‐1 signaling axis. These findings indicated that PDAP1 inhibition is warranted for CRC patients with PDAP1 overexpression.