Investigation of G-quadruplex formation in the FGFR2 promoter region and   its transcriptional regulation by liensinine

doi:10.1016/j.bbagen.2017.01.028

CORC > 北京大学 > 化学与分子工程学院

	Investigation of G-quadruplex formation in the FGFR2 promoter region and its transcriptional regulation by liensinine
	Zhang, Lulu ; Tan, Wei ; Zhou, Jiang ; Xu, Ming ; Yuan, Gu
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
	2017
关键词	FGFR2 G-quadruplex Liensinine Breast cancer Gene inhibitor GENOME-WIDE ASSOCIATION GROWTH IN-VITRO BREAST-CANCER OSTEOGENIC DIFFERENTIATION MASS-SPECTROMETRY STEM-CELLS DNA FAMILY SUSCEPTIBILITY RECOGNITION
DOI	10.1016/j.bbagen.2017.01.028
英文摘要	Background: Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in breast cancer tissues and cells, and has been shown to be a susceptibility factor for breast cancer. In this study, we found that the G-rich sequences in the FGFR2 promoter region can form G-quadruplexes, which could be the target and inhibitor of the FGFR2 gene. Methods: Initially, the formation of G-quadruplexes was confirmed by ESI-MS and CD, and DMS footprinting experiments gave the folding pattern of the G-quadruplexes. After luciferase reporter assays revealed that the Gquadruplex could inhibit the activity of the FGFR2 promoter, MS and SPR showed binding affinity and selectivity of the ligand. Then cell culture experiments and ChIP assay showed the bioactivity of the ligand. Results: We found that three G-rich sequences (S1-S3) in the FGFR2 promoter region can form G-quadruplex structures. And a natural alkaloid, liensinine, was found to bind to the S1 G-quadruplex with relative high affinity and selectivity. Cell culture experiments showed that liensinine inhibits FGFR2 activity at both the transcriptional and translational levels. Moreover, chromatin immunoprecipitation assay (ChIP) results showed that liensinine blocks the binding of E2F1 at the transcription factor binding site (TFBS) in the S1 sequence, which is the mechanism through which liensinine inhibits the FGFR2 gene. Conclusions: A natural alkaloid was discovered to selectively bind to the S1 G-quadruplex with relative high affinity, and therefore inhibited FGFR2 transcription and translation. General significance: Our discovery offers a useful strategy to inhibit FGFR2 transcription, i.e., targeting the Gquadruplex with a natural alkaloid.(C) 2017 Elsevier B.V. All rights reserved.; 973 Program [2012CB720600, 2012CB720601]; National Natural Science Foundation of China [21572016, 21372021, 91339105]; Beijing Municipal Science and Technology Commission [Z141100000214006]; Beijing Natural Science Foundation [7142165]; SCI(E); ARTICLE; 4; 884-891; 1861
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/474327]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Zhang, Lulu,Tan, Wei,Zhou, Jiang,et al. Investigation of G-quadruplex formation in the FGFR2 promoter region and its transcriptional regulation by liensinine[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,2017.
APA	Zhang, Lulu,Tan, Wei,Zhou, Jiang,Xu, Ming,&Yuan, Gu.(2017).Investigation of G-quadruplex formation in the FGFR2 promoter region and its transcriptional regulation by liensinine.BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS.
MLA	Zhang, Lulu,et al."Investigation of G-quadruplex formation in the FGFR2 promoter region and its transcriptional regulation by liensinine".BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS (2017).