The MYC Paralog-PARP1 Axis as a Potential TherapeuticTarget in MYC Paralog-Activated Small Cell Lung Cancer

doi:10.3389/fonc.2020.565820

	The MYC Paralog-PARP1 Axis as a Potential TherapeuticTarget in MYC Paralog-Activated Small Cell Lung Cancer
	Bian, Xing 1,2,8,9; Wang, Xiaolin 1,2,8,9; Zhang, Qiuyan 3; Ma, Liying 1,2,8,9; Cao, Guozhen 1,2,8,9; Xu, Ao 4,5; Han, Jinhua 6,7; Huang, Jun 6,7; Lin, Wenchu 2,8,9
刊名	FRONTIERS IN ONCOLOGY
	2020-10-08
卷号	10
关键词	small cell lung cancer MYCparalog PARP1 BET DNA damage response
ISSN号	2234-943X
DOI	10.3389/fonc.2020.565820
通讯作者	Lin, Wenchu(wenchu@hmfl.ac.cn)
英文摘要	Poly (ADP-ribose) polymerase 1 (PARP1) is highly expressed in small cell lung cancer (SCLC) and has emerged as an attractive target for treatment of SCLC. However, the clinical significance of PARP1 expression in SCLC remains elusive. In this study, we showed that high PARP1 expression was associated with better overall survival (OS), and was positively correlated with the expression of MYC paralogs in patients with SCLC. We demonstrated that PARP1 was transcriptionally regulated by MYC paralogs. Integrative analysis of multiple RNA-seq data sets indicated that DNA damage response (DDR) genes involved in the replication stress response (RSR) and homologous recombination (HR) repair pathways were highly enriched in MYC paralog-addicted SCLC cell models and in human SCLC specimens. Targeting the MYC paralog-PARP1 axis with concomitant BET and PARP inhibition resulted in synergistic effects in MYC paralog-activated SCLC. Our study identified a critical PARP1 regulatory pathway, and provided evidence for a rational combination treatment strategy for MYC paralog-activated SCLC.
资助项目	National Natural Science Foundation of China[81972191] ; National Natural Science Foundation of China[81672647] ; Science and Technology Service Network Initiative of Chinese Academy of Sciences[KFJ-STS-SCYD-010] ; Science and Technology Major Project of Anhui Province[18030801140] ; Key program of 13th five-year plan of CASHIPS[KP-2017-26] ; 100-Talent Program of Chinese Academy of Sciences
WOS关键词	PARP INHIBITORS ; DNA ; PATHWAY ; GENE ; MUTATIONS ; TARGETS ; STRESS ; DRIVEN
WOS研究方向	Oncology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000580545700001
资助机构	National Natural Science Foundation of China ; Science and Technology Service Network Initiative of Chinese Academy of Sciences ; Science and Technology Major Project of Anhui Province ; Key program of 13th five-year plan of CASHIPS ; 100-Talent Program of Chinese Academy of Sciences
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/104633]
专题	中国科学院合肥物质科学研究院
通讯作者	Lin, Wenchu
作者单位	1.Univ Sci & Technol China, Hefei, Peoples R China 2.High Magnet Field Lab Anhui Prov, Hefei, Peoples R China 3.Univ Sci & Technol China, Sch Life Sci, Innovat Ctr Cell Signaling Network, CAS Key Lab Innate Immun & Chron Dis, Hefei, Peoples R China 4.Univ Sci & Technol China, Div Life Sci & Med, Affiliated Hosp 1, Hefei, Peoples R China 5.Anhui Prov Hosp, Dept Pathol, Hefei, Peoples R China 6.Zhejiang Univ, MOE Key Lab Biosyst Homeostasis & Protect, Hangzhou, Peoples R China 7.Zhejiang Univ, Innovat Ctr Cell Signaling Network, Hangzhou, Peoples R China 8.Chinese Acad Sci, High Field Magnet Lab, Hefei, Peoples R China 9.Chinese Acad Sci, Hefei Inst Phys Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei, Peoples R China
推荐引用方式 GB/T 7714	Bian, Xing,Wang, Xiaolin,Zhang, Qiuyan,et al. The MYC Paralog-PARP1 Axis as a Potential TherapeuticTarget in MYC Paralog-Activated Small Cell Lung Cancer[J]. FRONTIERS IN ONCOLOGY,2020,10.
APA	Bian, Xing.,Wang, Xiaolin.,Zhang, Qiuyan.,Ma, Liying.,Cao, Guozhen.,...&Lin, Wenchu.(2020).The MYC Paralog-PARP1 Axis as a Potential TherapeuticTarget in MYC Paralog-Activated Small Cell Lung Cancer.FRONTIERS IN ONCOLOGY,10.
MLA	Bian, Xing,et al."The MYC Paralog-PARP1 Axis as a Potential TherapeuticTarget in MYC Paralog-Activated Small Cell Lung Cancer".FRONTIERS IN ONCOLOGY 10(2020).