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PAICS, a De Novo Purine Biosynthetic Enzyme, Is Overexpressed in Pancreatic Cancer and Is Involved in Its Progression

التفاصيل البيبلوغرافية
العنوان: PAICS, a De Novo Purine Biosynthetic Enzyme, Is Overexpressed in Pancreatic Cancer and Is Involved in Its Progression
المؤلفون: Donald J. Buchsbaum, Sumit Agarwal, Dafydd G. Thomas, Nirzari Gupta, Patsy G. Oliver, Isam-Eldin Eltoum, Hyung-Gyoon Kim, Sai Akshaya Hodigere Balasubramanya, Upender Manne, Kevin Hale, Sooryanarayana Varambally, Balabhadrapatruni V. S. K. Chakravarthi
المصدر: Translational Oncology
Translational Oncology, Vol 13, Iss 7, Pp 100776-(2020)
بيانات النشر: Neoplasia Press, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Original article, endocrine system diseases, Cell growth, Biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, lcsh:RC254-282, digestive system diseases, BET inhibitor, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Downregulation and upregulation, Pancreatic tumor, Cell culture, RNA interference, 030220 oncology & carcinogenesis, Pancreatic cancer, medicine, Cancer research, Immunohistochemistry
الوصف: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with an extremely poor prognosis. There is an urgent need to identify new therapeutic targets and also understand the mechanism of PDAC progression that leads to aggressiveness of the disease. To find therapeutic targets, we analyzed data related to PDAC transcriptome sequencing and found overexpression of the de novo purine metabolic enzyme phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS). Immunohistochemical analysis of PDAC tissues showed high expression of the PAICS protein. To assess the biological roles of PAICS, we used RNA interference and knock down of its expression in PDAC cell lines that caused a reduction in PDAC cell proliferation and invasion. Furthermore, results of chorioallantoic membrane assays and pancreatic cancer xenografts demonstrated that PAICS regulated pancreatic tumor growth. Our data also showed that, in PDAC cells, microRNA-128 regulates and targets PAICS. PAICS depletion in PDAC cells caused upregulation in E-cadherin, a marker of the epithelial-mesenchymal transition. In PDAC cells, a BET inhibitor, JQ1, reduced PAICS expression. Thus, our investigations show that PAICS is a therapeutic target for PDAC and, as an enzyme, is amenable to targeting by small molecules.
اللغة: English
تدمد: 1936-5233
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64d4241b8da10e165d21b54554a0b4f5
http://europepmc.org/articles/PMC7229293
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....64d4241b8da10e165d21b54554a0b4f5
قاعدة البيانات: OpenAIRE
الوصف
تدمد:19365233