دورية أكاديمية
أعرض في EDS

CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10.

التفاصيل البيبلوغرافية
العنوان: CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10.
المؤلفون: Kong D; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Wu Y; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China; The Second Medical College, Binzhou Medical University, Yantai, China., Tong B; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Liang Y; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Xu F; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Chi X; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Ni L; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Tian G; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Zhang G; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China., Xu Z; Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China. Electronic address: zhaoweixv@bzmc.edu.cn.
المصدر: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Aug; Vol. 1870 (6), pp. 167214. Date of Electronic Publication: 2024 May 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: Cellular Senescence*/drug effects , Aldo-Keto Reductases*/metabolism , Aldo-Keto Reductases*/genetics , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/metabolism , Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/drug therapy , Carcinoma, Pancreatic Ductal*/pathology , Carcinoma, Pancreatic Ductal*/metabolism , Carcinoma, Pancreatic Ductal*/genetics , Carcinoma, Pancreatic Ductal*/drug therapy , Gemcitabine* , Gene Expression Regulation, Neoplastic*/drug effects , Aldehyde Reductase*/metabolism , Aldehyde Reductase*/genetics , Aldehyde Reductase*/antagonists & inhibitors, Humans ; Cell Line, Tumor ; Animals ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Cell Proliferation ; Mice ; Oleanolic Acid/pharmacology ; Oleanolic Acid/analogs & derivatives ; Carcinogenesis/metabolism ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Mice, Nude
مستخلص: Pancreatic ductal adenocarcinoma (PDAC), is characteristic by a heterogeneous tumor microenvironment and gene mutations, conveys a dismal prognosis and low response to chemotherapy and immunotherapy. Here, we found that checkpoint suppressor 1 (CHES1) served as a tumor repressor in PDAC and was associated with patient prognosis. Functional experiments indicated that CHES1 suppressed the proliferation and invasion of PDAC by modulating cellular senescence. To further identify the downstream factor of CHES1 in PDAC, label-free quantitative proteomics analysis was conducted, which showed that the oncogenic Aldo-keto reductase 1B10 (AKR1B10) was transcriptionally repressed by CHES1 in PDAC. And AKR1B10 facilitated the malignant activity and repressed senescent phenotype of PDAC cells. Moreover, pharmaceutical inhibition of AKR1B10 with Oleanolic acid (OA) significantly induced tumor regression and sensitized PDAC cells to gemcitabine, and this combined therapy did not cause obvious side effects. Rescued experiments revealed that CHES1 regulated the tumorigenesis and gemcitabine sensitivity through AKR1B10-mediated senescence in PDAC. In summary, this study revealed that the CHES1/AKR1B10 axis modulated the progression and cellular senescence in PDAC, which might provide revenues for drug-targeting and senescence-inducing therapies for PDAC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: AKR1B10; CHES1; Gemcitabine; PDAC; Senescence
المشرفين على المادة: EC 1.1.1.- (AKR1B10 protein, human)
EC 1.1.1.- (Aldo-Keto Reductases)
0 (Gemcitabine)
EC 1.1.1.21 (Aldehyde Reductase)
0W860991D6 (Deoxycytidine)
6SMK8R7TGJ (Oleanolic Acid)
تواريخ الأحداث: Date Created: 20240508 Date Completed: 20240615 Latest Revision: 20240615
رمز التحديث: 20240616
DOI: 10.1016/j.bbadis.2024.167214
PMID: 38718846
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-260X
DOI:10.1016/j.bbadis.2024.167214