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dc.contributor.authorJie Wu
dc.contributor.authorChi Wang
dc.contributor.authorXilan Li
dc.contributor.authorYanling Song
dc.contributor.authorWei Wang
dc.contributor.authorCong Li
dc.contributor.authorJia Hu
dc.contributor.authorZhi Zhu
dc.contributor.authorJiuxing Li
dc.contributor.authorWeiyun Zhang
dc.contributor.authorZhongxian Lu
dc.contributor.authorChaoyong James Yang
dc.contributor.author杨朝勇
dc.date.accessioned2013-01-17T01:56:58Z
dc.date.available2013-01-17T01:56:58Z
dc.date.issued2012-09-28
dc.identifier.citationPLOS ONE,2012,7(9):e46393zh_CN
dc.identifier.issn1932-6203
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0046393
dc.identifier.uriWOS:000309973900153
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/14576
dc.description.abstractBackground: 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.zh_CN
dc.description.sponsorshipNational 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]zh_CN
dc.language.isoenzh_CN
dc.publisherPUBLIC LIBRARY SCIENCEzh_CN
dc.subjectCELL LUNG-CANCERzh_CN
dc.subjectRNA MOLECULESzh_CN
dc.subjectOLIGONUCLEOTIDE INHIBITORSzh_CN
dc.subjectEXPONENTIAL ENRICHMENTzh_CN
dc.subjectSYSTEMATIC EVOLUTIONzh_CN
dc.subjectPROSTATE-CANCERzh_CN
dc.subjectCEMENT GLANDzh_CN
dc.subjectAGR2zh_CN
dc.subjectBINDINGzh_CN
dc.subjectPROBESzh_CN
dc.titleIdentification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2zh_CN
dc.typeArticlezh_CN


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