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
Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribos...Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribosomal functions of RPs are rarely reported. Herein, we identified a ribosomal protein S7-interacting partner, BCCIPβ, which modulates the functional conversion of S7. Through the N-terminal acidic domain, BCCIPβ interacts with the central basic region in S7 and regulates the extraribosomal dis- tribution of S7. BCCIPI~ deficiency abrogates the ribosomal accumulation but enhances the ribosome-free location of S7. This translocation further impairs protein synthesis and triggers ribosomal stress. Consequently, BCCIPβ deficiency suppresses the ribosomal function and initiates the extraribosomal function of S7, resulting in restriction of cell proliferation. Moreover, clinically relevant S7 mutations were found to dampen the interaction with BCCIPβ and facilitate the functional transition of S7. In conclu- sion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomai functions of S7 and has implica- tions in cell growth and tumor development.展开更多
Cyprinidae is the largest fish family in the world and contains about 210 genera and 2010 species. Appropriate DNA markers must be selected for the phylogenetic analyses of Cyprinidae. In present study, the 1st intron...Cyprinidae is the largest fish family in the world and contains about 210 genera and 2010 species. Appropriate DNA markers must be selected for the phylogenetic analyses of Cyprinidae. In present study, the 1st intron of the S7 ribosomal protein (r-protein) gene is first used to examine the relationships among cyprinid fishes. The length of the 1st intron obtained by PCR amplification ranges from 655 to 859 bp in the 16 cyprinid species investigated, and is 602 bp in Myxocyprinus asiaticus. Out of the alignment of 925 nucleotide sites obtained, the parsimony informative sites are 499 and occupy 54% of the total sites. The results indicate that the 1st intron sequences of the S7 r-protein gene in cyprinids are rich in informative sites and vary remarkably in sequence divergence from 2.3% between close species to 66.6% between distant species. The bootstrap values of the interior nodes in the NJ (neighbor-joining) and MP (most-parsimony) trees based on the present S7 r-protein gene data are higher than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.
文摘Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribosomal functions of RPs are rarely reported. Herein, we identified a ribosomal protein S7-interacting partner, BCCIPβ, which modulates the functional conversion of S7. Through the N-terminal acidic domain, BCCIPβ interacts with the central basic region in S7 and regulates the extraribosomal dis- tribution of S7. BCCIPI~ deficiency abrogates the ribosomal accumulation but enhances the ribosome-free location of S7. This translocation further impairs protein synthesis and triggers ribosomal stress. Consequently, BCCIPβ deficiency suppresses the ribosomal function and initiates the extraribosomal function of S7, resulting in restriction of cell proliferation. Moreover, clinically relevant S7 mutations were found to dampen the interaction with BCCIPβ and facilitate the functional transition of S7. In conclu- sion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomai functions of S7 and has implica- tions in cell growth and tumor development.
基金This work was supported by the Chinese Academy of Sciences (Grant No. KSCX2-SW-101B)the National Natural Science Foundation of China (Grant No. 39830050).
文摘Cyprinidae is the largest fish family in the world and contains about 210 genera and 2010 species. Appropriate DNA markers must be selected for the phylogenetic analyses of Cyprinidae. In present study, the 1st intron of the S7 ribosomal protein (r-protein) gene is first used to examine the relationships among cyprinid fishes. The length of the 1st intron obtained by PCR amplification ranges from 655 to 859 bp in the 16 cyprinid species investigated, and is 602 bp in Myxocyprinus asiaticus. Out of the alignment of 925 nucleotide sites obtained, the parsimony informative sites are 499 and occupy 54% of the total sites. The results indicate that the 1st intron sequences of the S7 r-protein gene in cyprinids are rich in informative sites and vary remarkably in sequence divergence from 2.3% between close species to 66.6% between distant species. The bootstrap values of the interior nodes in the NJ (neighbor-joining) and MP (most-parsimony) trees based on the present S7 r-protein gene data are higher than
