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针对乳腺癌中扩增癌基因的DNA适配体的筛选与应用1。

Selection and Application of DNA Aptamer Against Oncogene Amplified in Breast Cancer 1.

作者信息

An Yuan, Wu Jie, Yang Bo, Zhu Zhi, Gao Mingxuan, Yu Chundong, Yang Chaoyong James

机构信息

State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Collaborative Innovation Center of Chemistry for Energy Materials, Key Laboratory for Chemical Biology of Fujian Province, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, People's Republic of China.

出版信息

J Mol Evol. 2015 Dec;81(5-6):179-85. doi: 10.1007/s00239-015-9703-y. Epub 2015 Oct 12.

Abstract

Amplified in breast cancer 1 (AIB1), also known as steroid receptor coactivator 3 (SRC-3), is a transcriptional coactivator that interacts with nuclear receptors and other transcription factors to enhance their effects on target gene transcription. AIB1, which acts as a major oncogene, is highly expressed in many human cancers, and has been demonstrated to be a key regulator for tumor initiation, progression, metastasis, invasion, and survival. Recruitment of the transcriptional factor CBP/p300 by CBP/p300-interaction domain (CID) of AIB1 is essential for its transcriptional activation function. In this research, we isolated a DNA aptamer AY-3 that binds to AIB1-CID from a random oligonucleotide library using in vitro screening technology-Systematic Evolution of Ligands by EXponential enrichment (SELEX). The binding affinity of the aptamer to AIB1-CID fusion protein is in the nanomolar range. More importantly, the aptamer was found to disrupt in the interaction between p300 and AIB1. This aptamer has great potential to serve as a therapeutic agent for cancer by inhibiting the coactivation of AIB1.

摘要

乳腺癌中扩增基因1(AIB1),也被称为类固醇受体辅激活因子3(SRC-3),是一种转录辅激活因子,它与核受体及其他转录因子相互作用,以增强它们对靶基因转录的影响。AIB1作为一种主要的癌基因,在许多人类癌症中高表达,并且已被证明是肿瘤起始、进展、转移、侵袭及存活的关键调节因子。AIB1的CBP/p300相互作用结构域(CID)募集转录因子CBP/p300对其转录激活功能至关重要。在本研究中,我们使用体外筛选技术——指数富集的配体系统进化技术(SELEX),从随机寡核苷酸文库中分离出一种与AIB1-CID结合的DNA适配体AY-3。该适配体与AIB1-CID融合蛋白的结合亲和力处于纳摩尔范围。更重要的是,发现该适配体可破坏p300与AIB1之间的相互作用。这种适配体具有通过抑制AIB1的共激活作用而作为癌症治疗药物的巨大潜力。

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