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 dis...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.展开更多
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).
文摘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.
