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

doi:10.1038/s41419-022-05254-1

	Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer
	Yuan, Yuan 1; Zhang, Xiaojing 1; Du, Kaining 1; Zhu, Xiaohui 2; Chang, Shanshan 1; Chen, Yang 1; Xu, Yidan 1; Sun, Jiachun 3,4; Luo, Xiaonuan 1; Deng, Shiqi 1; Qin, Ying 5; Feng, Xianling 1; Wei, Yanjie 6; Fan, Xinmin 1; Liu, Ziyang 1; Zheng, Baixin 1; Ashktorab, Hassan 7,8; Smoot, Duane 9; Li, Song 10; Xie, Xiaoxun 11; Jin, Zhe 1; Peng, Yin 1
	2022-09-27
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	13 期号:9 页码:15
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.
DOI	10.1038/s41419-022-05254-1
收录类别	SCI
语种	英语
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
WOS类目	Cell Biology
WOS记录号	WOS:000862655300003
出版者	SPRINGERNATURE
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/19819
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.Shenzhen Univ Hlth Sci Ctr, Dept Pathol, Guangdong Prov Key Lab Genome Stabil & Dis Preven, Shenzhen 518060, Guangdong, Peoples R China 2.Shenzhen Technol Univ, Dept Pharmacol, Coll Pharm, Shenzhen 518118, Guangdong, Peoples R China 3.Henan Univ Sci & Technol, Henan Key Lab Canc Epigenet, Affiliated Hosp 1, 24,Jinhua Rd, Jinhua 471003, Henan, Peoples R China 4.Henan Univ Sci & Technol, Henan Key Lab Canc Epigenet, Coll Clin Med, 24,Jinhua Rd, Jinhua 471003, Henan, Peoples R China 5.Shenzhen Univ, Shenzhen Second Peoples Hosp, Dept Gastrointestinal Surg, Affiliated Hosp 1, Shenzhen 518000, Guangdong, Peoples R China 6.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518000, Guangdong, Peoples R China 7.Howard Univ, Dept Med, Washington, DC 20060 USA 8.Howard Univ, Coll Med, Ctr Canc, Washington, DC 20060 USA 9.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA 10.Shenzhen Sci & Technol Dev Exchange Ctr, Shenzhen 518055, Guangdong, Peoples R China 11.Guangxi Med Univ, Sch Basic Med Sci, Nanning 530021, 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.