p53 inhibits the Urea cycle and represses polyamine biosynthesis in glioma cell lines

作者全名："Zhao, Yuhong; Chen, Yingxi; Wei, Ling; Ran, Jianhua; Wang, Kejian; Zhu, Shujuan; Liu, Qian"

作者地址："[Zhao, Yuhong; Wei, Ling; Ran, Jianhua; Wang, Kejian; Zhu, Shujuan; Liu, Qian] Chongqing Med Univ, Basic Med Coll, Inst Neurosci, Chongqing 400016, Peoples R China; [Chen, Yingxi; Liu, Qian] Chongqing Coll Tradit Chinese Med, Dept Basic Med, Chongqing 402760, Peoples R China"

通信作者："Liu, Q (通讯作者)，Chongqing Med Univ, Basic Med Coll, Inst Neurosci, Chongqing 400016, Peoples R China.; Liu, Q (通讯作者)，Chongqing Coll Tradit Chinese Med, Dept Basic Med, Chongqing 402760, Peoples R China."

来源：METABOLIC BRAIN DISEASE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000926357700001

JCR分区：Q2

影响因子：3.2

年份：2023

卷号：38

期号：4

开始页：1143

结束页：1153

文献类型：Article

关键词：Glioma; p53; Urea cycle; Ornithine decarboxylase; Polyamine

摘要："Glioma is the most common malignant tumor of the central nervous system. The urea cycle (UC) is an essential pathway to convert excess nitrogen and ammonia into the less toxic urea in humans. However, less is known about the functional significance of the urea cycle in glioma. p53 functions as a tumor suppressor and modulates several cellular functions and disease processes. In the present study, we aimed to explore whether p53 influences glioma progression by regulating the urea cycle. Here, we demonstrated the inhibitory impact of p53 on the expression of urea cycle enzymes and urea genesis in glioma cells. The level of polyamine, a urea cycle metabolite, was also regulated by p53 in glioma cells. Carbamoyl phosphate synthetase-1 (CPS1) is the first key enzyme involved in the urea cycle. Functionally, we demonstrated that CPS1 knockdown suppressed glioma cell proliferation, migration and invasion. Mechanistically, we demonstrated that the expression of ornithine decarboxylase (ODC), which determines the generation of polyamine, was regulated by CPS1. In addition, the impacts of p53 knockdown on ODC expression, glioma cell growth and aggressive phenotypes were significantly reversed by CPS1 inhibition. In conclusion, these results demonstrated that p53 inhibits polyamine metabolism by suppressing the urea cycle, which inhibits glioma progression."

基金机构：Natural Science Foundation of Chongqing Science and Technology Bureau [cst-c2020jcyj-msxmX0387]; Yuzhong Science and Technology Bureau of Chongqing [2020115]

基金资助正文："This work was supported by the Natural Science Foundation of Chongqing Science and Technology Bureau (Grant/award No: #cst-c2020jcyj-msxmX0387), Yuzhong Science and Technology Bureau of Chongqing (Grant/award No: #2020115)."