南方科技大学知识苑(SUSTech KC): Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer

题名	Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer
作者	Wang, Yan; Zuo, Min; Jin, Hongtao; Lai, Meina; Luo, Jinfeng; Cheng, Zhiqiang
通讯作者	Cheng, Zhiqiang
发表日期	2020-08-19
DOI	10.1080/10799893.2020.1808676
发表期刊	J RECEPT SIGNAL TR R 影响因子和分区
ISSN	1079-9893
EISSN	1532-4281
卷号	41 期号:3
摘要	Background E74 Like ETS Transcription Factor 3 (ELF3) functions as a transcriptional factor to regulate non-small cell lung cancer (NSCLC) differentiation and progression. Poly(ADP-ribose) polymerase (PARP) inhibitors demonstrate anti-tumor effect in NSCLC. This study aimed to investigate whether ELF3 confers synthetic lethal with PARP inhibitor in NSCLC. Materials and methods The sensitivity of PARP inhibitor, Olaparib, to different NSCLC cell lines was determined by half maximal inhibitory concentration (IC50). Expression of ELF3 in NSCLC cell lines was evaluated by western blot. The effects of ELF3 on cytotoxicity of Olaparib to NSCLC were investigated by MTT (3-(4,5- di methyl thiazol -2-yl)-2,5-di phenyl tetrazolium bromide) and colony formation assays. The underlying mechanism involved in synthetic lethality with ELF3 and PARP inhibitors in NSCLC were detected by immunofluorescence and Western blot. Results ELF3 was up-regulated in NSCLC cell lines exhibiting resistance to PARP inhibitor, Olaparib. Knock down of ELF3 decreased the sensitivity and enhanced cytotoxicity of Olaparib to NSCLC cells. Moreover, knock down of ELF3 increased S139 phosphorylated histone H2AX (gamma H2AX), and inhibited homologous recombination activityviadown-regulation of DNA repair protein RAD51 homolog 1 (RAD51), thus showing deficiency in DNA damage repair. Over-expression of ELF3 could up-regulate phosphorylation of AKT (Protein kinase B), while knock down of ELF3 regulated homologous recombination-mediated DNA repairviadown-regulation of phosphorylation of AKT. Conclusion Knock down of ELF3 revealed homologous recombination deficiencyviaAKT signaling pathway, and synthetic lethality with ELF3 inhibition and PARP inhibitor indicated the clinical significance of PARP inhibitor in ELF3-deficient NSCLC.
关键词	ELF3 ETS TRANSCRIPTION FACTOR PARP DNA-DAMAGE RESPONSE synthetic lethal ESE-1 sensitivity RESISTANCE AKT REPAIR DRUGS
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	第一 ; 通讯
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000561081300001
出版者	TAYLOR & FRANCIS LTD
来源库	Web of Science
引用统计	被引频次[WOS]：4
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/187589
专题	南方科技大学第一附属医院
作者单位	Southern Univ Sci & Technol, Affiliated Hosp 1, Jinan Univ, Dept Pathol,Shenzhen Peoples Hosp,Clin Med Coll 2, 1017 Dongmen North Rd, Shenzhen, Guangdong, Peoples R China
第一作者单位	南方科技大学第一附属医院
通讯作者单位	南方科技大学第一附属医院
第一作者的第一单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Wang, Yan,Zuo, Min,Jin, Hongtao,et al. Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer[J]. J RECEPT SIGNAL TR R,2020,41(3).
APA	Wang, Yan,Zuo, Min,Jin, Hongtao,Lai, Meina,Luo, Jinfeng,&Cheng, Zhiqiang.(2020).Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer.J RECEPT SIGNAL TR R,41(3).
MLA	Wang, Yan,et al."Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer".J RECEPT SIGNAL TR R 41.3(2020).