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Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer

文献类型：期刊论文

作者Yuan, Yuan11; Zhang, Xiaojing11; Du, Kaining11; Zhu, Xiaohui10; Chang, Shanshan11; Chen, Yang11; Xu, Yidan11; Sun, Jiachun8,9; Luo, Xiaonuan11; Deng, Shiqi11
刊名CELL DEATH & DISEASE
出版日期2022-09-27
卷号13期号:9页码:15
ISSN号2041-4889
DOI10.1038/s41419-022-05254-1
英文摘要Circular RNAs (circRNAs) have been reported to play essential roles in tumorigenesis and progression. This study aimed to identify dysregulated circRNAs in gastric cancer (GC) and investigate the functions and underlying mechanism of these circRNAs in GC development. Here, we identify circ_CEA, a circRNA derived from the back-splicing of CEA cell adhesion molecule 5 (CEA) gene, as a novel oncogenic driver of GC. Circ_CEA is significantly upregulated in GC tissues and cell lines. Circ_CEA knockdown suppresses GC progression, and enhances stress-induced apoptosis in vitro and in vivo. Mechanistically, circ_CEA interacts with p53 and cyclin-dependent kinases 1 (CDK1) proteins. It serves as a scaffold to enhance the association between p53 and CDK1. As a result, circ_CEA promotes CDK1-mediated p53 phosphorylation at Ser315, then decreases p53 nuclear retention and suppresses its activity, leading to the downregulation of p53 target genes associated with apoptosis. These findings suggest that circ_CEA protects GC cells from stress-induced apoptosis, via acting as a protein scaffold and interacting with p53 and CDK1 proteins. Combinational therapy of targeting circ_CEA and chemo-drug caused more cell apoptosis, decreased tumor volume and alleviated side effect induced by chemo-drug. Therefore, targeting circ_CEA might present a novel treatment strategy for GC.
资助项目National Natural Science Foundation of China[82172946] ; National Natural Science Foundation of China[82173290] ; National Natural Science Foundation of China[81772592] ; National Natural Science Foundation of China[31601028] ; National Natural Science Foundation of China[81871969] ; Natural Science Foundation of Guangdong province[2022A1515010706] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; Shenzhen University Talent program[000324] ; SZU Top Ranking Project[860-00000210] ; National Key Research and Development Program of China[2016YFB0201305] ; Youth talent support program in medical center Shenzhen University
WOS研究方向Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000862655300003
源URL[http://119.78.100.204/handle/2XEOYT63/19818]  
专题中国科学院计算技术研究所期刊论文
通讯作者Peng, Yin
作者单位1.Guangxi Med Univ, Sch Basic Med Sci, Nanning 530021, Peoples R China
2.Shenzhen Sci & Technol Dev Exchange Ctr, Shenzhen 518055, Guangdong, Peoples R China
3.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA
4.Howard Univ, Coll Med, Ctr Canc, Washington, DC 20060 USA
5.Howard Univ, Dept Med, Washington, DC 20060 USA
6.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518000, Guangdong, Peoples R China
7.Shenzhen Univ, Shenzhen Second Peoples Hosp, Dept Gastrointestinal Surg, Affiliated Hosp 1, Shenzhen 518000, Guangdong, Peoples R China
8.Henan Univ Sci & Technol, Henan Key Lab Canc Epigenet, Coll Clin Med, 24,Jinhua Rd, Jinhua 471003, Henan, Peoples R China
9.Henan Univ Sci & Technol, Henan Key Lab Canc Epigenet, Affiliated Hosp 1, 24,Jinhua Rd, Jinhua 471003, Henan, Peoples R China
10.Shenzhen Technol Univ, Dept Pharmacol, Coll Pharm, Shenzhen 518118, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 Yuan, Yuan,Zhang, Xiaojing,Du, Kaining,et al. Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer[J]. CELL DEATH & DISEASE,2022,13(9):15.
APA Yuan, Yuan.,Zhang, Xiaojing.,Du, Kaining.,Zhu, Xiaohui.,Chang, Shanshan.,...&Peng, Yin.(2022).Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer.CELL DEATH & DISEASE,13(9),15.
MLA Yuan, Yuan,et al."Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer".CELL DEATH & DISEASE 13.9(2022):15.

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