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作 者:Yunyi Liu Juan Li Hailong Ou Dan Qi Bei Hu Yuxi Xu Jian Hu Yi Xiong Luling Xia Jason HHuang Xiaoxiao Hu Erxi Wu
机构地区:[1]State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Biology,Molecular Science and Biomedicine Laboratory and Aptamer Engineering Center of Hunan Province,Hunan University,Changsha,Hunan 410082,China [2]Shenzhen Research Institute,Hunan University,Shenzhen,Guangdong 518000,China [3]Department of Neurosurgery and Neuroscience Institute,Baylor Scott&White Health,Temple,TX 76508,USA [4]Department of Respiratory Medicine,The Third Xiangya Hospital,Central South University,Changsha,Hunan 410013,China [5]Texas A&M University School of Medicine,College Station,TX 77843,USA [6]Texas A&M University School of Pharmacy,College Station,TX 77843,USA [7]LIVESTRONG Cancer Institutes and Department of Oncology,Dell Medical School,The University of Texas at Austin,Austin,TX 78712,USA [8]Greater Bay Area Institute for Innovation,Hunan University,Guangzhou,Guangdong 511300,China
出 处:《Genes & Diseases》2023年第5期2137-2150,共14页基因与疾病(英文)
基 金:supported by the National Natural Science Foundation of China(No.31970692)(X.Hu);the Corbett Estate Fund for Cancer Research(USA)(No.62285-531021-41800,62285-531021-51800,62285-531021-61800,and 62285-531021-71800)(E.Wu).
摘 要:Aptamers,short single DNA or RNA oligonucleotides,have shown immense application potential as molecular probes for the early diagnosis and therapy of cancer.However,conventional cell-SELEX technologies for aptamer discovery are time-consuming and laborious.Here we discovered a new aptamer BC-3 by using an improved rapid X-Aptamer selection process for human bladder carcinoma,for which there is no specific molecular probe yet.We show that BC-3 exhibited excellent affinity in bladder cancer cells but not normal cells.We demonstrate that BC-3 displayed high selectivity for tumor cells over their normal counterparts in vitro,in mice,and in patient tumor tissue specimens.Further endocytosis pathway analysis revealed that BC-3 internalized into bladder cancer cells via clathrin-mediated endocytosis.Importantly,we identified ribosomal protein S7(RPS7)as the binding target of BC-3 via an integrated methodology(mass spectrometry,colocalization assay,and immunoblotting).Together,we report that a novel aptamer BC-3 is discovered for bladder cancer and its properties in the disease are unearthed.Our findings will facilitate the discovery of novel diagnostic and therapeutic strategies for bladder cancer.
关 键 词:Bladder cancer Cell-SELEX Clathrin-mediated endocytosis Intracellular colocalization Ribosomal protein S7 X-aptamer selections
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