QQ客服 官方微博 反馈留言

	Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2
	Jie Wu ; Chi Wang ; Xilan Li ; Yanling Song ; Wei Wang ; Cong Li ; Jia Hu ; Zhi Zhu ; Jiuxing Li ; Weiyun Zhang ; Zhongxian Lu ; Chaoyong James Yang ; Yang CY(杨朝勇)
	2012-09-28
关键词	CELL LUNG-CANCER RNA MOLECULES OLIGONUCLEOTIDE INHIBITORS EXPONENTIAL ENRICHMENT SYSTEMATIC EVOLUTION PROSTATE-CANCER CEMENT GLAND AGR2 BINDING PROBES
英文摘要	Background: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism. Methodology/Principal Findings: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K-d values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2. Conclusion/Significance: In this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.; National Basic Research Program of China [2010CB732402]; National Instrumentation Program [2011YQ03012412]; Natural Science Foundation of Fujian Province for Distinguished Young Scholars [2010 J06004]; National Found for Fostering Talents of Basic Science [J1030415]
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1371/journal.pone.0046393]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Jie Wu,Chi Wang,Xilan Li,et al. Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2[J],2012.
APA	Jie Wu.,Chi Wang.,Xilan Li.,Yanling Song.,Wei Wang.,...&杨朝勇.(2012).Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2..
MLA	Jie Wu,et al."Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2".(2012).

个性服务

查看访问统计

相关权益政策

暂无数据

收藏/分享

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。