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Martin E Gleave - One of the best experts on this subject based on the ideXlab platform.
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synergistic chemosensitization and inhibition of progression to androgen independence by Antisense bcl 2 oligodeoxynucleotide and paclitaxel in the lncap prostate tumor model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that Antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate tumor model. The objectives in this study were to determine whether Antisense human Bcl-2 ODN enhances chemosensitivity of paclitaxel and whether combined Antisense Bcl-2 ODN and paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP tumor model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with Antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM Antisense Bcl-2 ODN and 1 nM paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined Antisense Bcl-2 and polymeric micellar paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP tumors compared with either agent alone. By 15 weeks post castration, tumor volume in mice treated with Antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel was >3-fold higher than in mice treated with combined Antisense Bcl-2 ODN and paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with Antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel but remained 90% below the pre-castration level in mice treated with combined Antisense Bcl-2 ODN and paclitaxel. These findings identify combined Antisense Bcl-2 and paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer. © 2001 Wiley-Liss, Inc.
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synergistic chemosensitization and inhibition of progression to androgen independence by Antisense bcl 2 oligodeoxynucleotide and paclitaxel in the lncap prostate tumor model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that Antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate tumor model. The objectives in this study were to determine whether Antisense human Bcl-2 ODN enhances chemosensitivity of paclitaxel and whether combined Antisense Bcl-2 ODN and paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP tumor model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with Antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM Antisense Bcl-2 ODN and 1 nM paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined Antisense Bcl-2 and polymeric micellar paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP tumors compared with either agent alone. By 15 weeks post castration, tumor volume in mice treated with Antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel was >3-fold higher than in mice treated with combined Antisense Bcl-2 ODN and paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with Antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel but remained 90% below the pre-castration level in mice treated with combined Antisense Bcl-2 ODN and paclitaxel. These findings identify combined Antisense Bcl-2 and paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer.
Isidre Ferrer - One of the best experts on this subject based on the ideXlab platform.
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long non coding Antisense rna controls uchl1 translation through an embedded sineb2 repeat
Nature, 2012Co-Authors: Claudia Carrieri, Laura Cimatti, Marta Biagioli, Anne Beugnet, Silvia Zucchelli, Stefania Fedele, Elisa Pesce, Isidre FerrerAbstract:Antisense Uchl1, a long non-coding RNA that is an Antisense transcript for the Uchl1 gene, upregulates UCHL1 protein levels through the combined action of an overlapping sequence at its 5′ end and an embedded SINEB2 element. Many of the RNAs transcribed from the genome have as yet no known function. One such long non-coding RNA (lncRNA) is an Antisense transcript for the ubiquitin carboxy-terminal hydrolase L1 (Uchl1) gene, which is involved in brain function and implicated in neurodegeneration. This study shows that the Antisense Uchl1 lncRNA recognizes a short interspersed nuclear element, SINEB2, within the Uchl1 gene. Interaction of Antisense Uchl1 with SINEB2 results in upregulation of UCHL1 expression at the translational level. Natural or synthetic Antisense transcripts with embedded repetitive elements may prove useful as tools to increase translation of selected messenger RNAs, and may have potential as RNA therapeutics. Most of the mammalian genome is transcribed1,2,3. This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function4. Antisense lncRNAs may form sense–Antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability5,6,7,8,9,10. Here we identify a nuclear-enriched lncRNA Antisense to mouse ubiquitin carboxy-terminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases11. Antisense Uchl1 increases UCHL1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs. Antisense Uchl1 activity depends on the presence of a 5′ overlapping sequence and an embedded inverted SINEB2 element. These features are shared by other natural Antisense transcripts and can confer regulatory activity to an artificial Antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as mTORC1 inhibition by rapamycin causes an increase in UCHL1 protein that is associated to the shuttling of Antisense Uchl1 RNA from the nucleus to the cytoplasm. Antisense Uchl1 RNA is then required for the association of the overlapping sense protein-coding mRNA to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.
136–141. Doi:10.1038/embor.2010.208 Cacchiarelli, D., Incitti, T., Martone, J., Cesana - One of the best experts on this subject based on the ideXlab platform.
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Long non-coding Antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat
Nature, 2012Co-Authors: 239. Doi:10.1186/1471-2105-10-239 Arrial, R. T., Togawa, R. C., & Brigido, M. De M. , 23. Doi:10.1002/0471142727.mb1300s82 Ausubel, F., Brent, R., Kingston, R., Moore, D., S, Mcb.01394–14. Doi:10.1128/mcb.01394-14 Ballarino, M., Cazzella, V., D’andrea, D., Grassi,, D. L. (2014). Long Non-coding Rnas: Modulators Of Nuclear Structure And Function. Current Opinion In Bergmann, J. H., & Spector, 327–336. Doi:10.1016/j.stem.2012.01.017 Boutet, S. C., Cheung, T. H., Quach, N. L., Liu, L, 645–673. Doi:10.1146/annurev.cellbio.23.090506.123438 Buckingham, M., & Relaix, F. (2007). The Role Of P, 225–238. Doi:10.1016/j.devcel.2013.12.020 Buckingham, M., & Rigby, P. W. J. (2014a). Gene Re, P. W. J. (2014b). Gene Regulatory Networks And Transcriptional Mechanisms That Control Myogenesis. D Buckingham, M., & Rigby, 1915–1927. Doi:10.1101/gad.17446611 Cabili, M., Trapnell, C., Goff, L., Koziol, M., Ta, 136–141. Doi:10.1038/embor.2010.208 Cacchiarelli, D., Incitti, T., Martone, J., CesanaAbstract:Most of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function. Antisense lncRNAs may form sense-Antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability. Here we identify a nuclear-enriched lncRNA Antisense to mouse ubiquitin carboxy-terminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases. Antisense Uchl1 increases UCHL1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs. Antisense Uchl1 activity depends on the presence of a 5' overlapping sequence and an embedded inverted SINEB2 element. These features are shared by other natural Antisense transcripts and can confer regulatory activity to an artificial Antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as mTORC1 inhibition by rapamycin causes an increase in UCHL1 protein that is associated to the shuttling of Antisense Uchl1 RNA from the nucleus to the cytoplasm. Antisense Uchl1 RNA is then required for the association of the overlapping sense protein-coding mRNA to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.
Marta Biagioli - One of the best experts on this subject based on the ideXlab platform.
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long non coding Antisense rna controls uchl1 translation through an embedded sineb2 repeat
Nature, 2012Co-Authors: Claudia Carrieri, Laura Cimatti, Marta Biagioli, Anne Beugnet, Silvia Zucchelli, Stefania Fedele, Elisa Pesce, Isidre FerrerAbstract:Antisense Uchl1, a long non-coding RNA that is an Antisense transcript for the Uchl1 gene, upregulates UCHL1 protein levels through the combined action of an overlapping sequence at its 5′ end and an embedded SINEB2 element. Many of the RNAs transcribed from the genome have as yet no known function. One such long non-coding RNA (lncRNA) is an Antisense transcript for the ubiquitin carboxy-terminal hydrolase L1 (Uchl1) gene, which is involved in brain function and implicated in neurodegeneration. This study shows that the Antisense Uchl1 lncRNA recognizes a short interspersed nuclear element, SINEB2, within the Uchl1 gene. Interaction of Antisense Uchl1 with SINEB2 results in upregulation of UCHL1 expression at the translational level. Natural or synthetic Antisense transcripts with embedded repetitive elements may prove useful as tools to increase translation of selected messenger RNAs, and may have potential as RNA therapeutics. Most of the mammalian genome is transcribed1,2,3. This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function4. Antisense lncRNAs may form sense–Antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability5,6,7,8,9,10. Here we identify a nuclear-enriched lncRNA Antisense to mouse ubiquitin carboxy-terminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases11. Antisense Uchl1 increases UCHL1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs. Antisense Uchl1 activity depends on the presence of a 5′ overlapping sequence and an embedded inverted SINEB2 element. These features are shared by other natural Antisense transcripts and can confer regulatory activity to an artificial Antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as mTORC1 inhibition by rapamycin causes an increase in UCHL1 protein that is associated to the shuttling of Antisense Uchl1 RNA from the nucleus to the cytoplasm. Antisense Uchl1 RNA is then required for the association of the overlapping sense protein-coding mRNA to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.
Silvia Zucchelli - One of the best experts on this subject based on the ideXlab platform.
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long non coding Antisense rna controls uchl1 translation through an embedded sineb2 repeat
Nature, 2012Co-Authors: Claudia Carrieri, Laura Cimatti, Marta Biagioli, Anne Beugnet, Silvia Zucchelli, Stefania Fedele, Elisa Pesce, Isidre FerrerAbstract:Antisense Uchl1, a long non-coding RNA that is an Antisense transcript for the Uchl1 gene, upregulates UCHL1 protein levels through the combined action of an overlapping sequence at its 5′ end and an embedded SINEB2 element. Many of the RNAs transcribed from the genome have as yet no known function. One such long non-coding RNA (lncRNA) is an Antisense transcript for the ubiquitin carboxy-terminal hydrolase L1 (Uchl1) gene, which is involved in brain function and implicated in neurodegeneration. This study shows that the Antisense Uchl1 lncRNA recognizes a short interspersed nuclear element, SINEB2, within the Uchl1 gene. Interaction of Antisense Uchl1 with SINEB2 results in upregulation of UCHL1 expression at the translational level. Natural or synthetic Antisense transcripts with embedded repetitive elements may prove useful as tools to increase translation of selected messenger RNAs, and may have potential as RNA therapeutics. Most of the mammalian genome is transcribed1,2,3. This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function4. Antisense lncRNAs may form sense–Antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability5,6,7,8,9,10. Here we identify a nuclear-enriched lncRNA Antisense to mouse ubiquitin carboxy-terminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases11. Antisense Uchl1 increases UCHL1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs. Antisense Uchl1 activity depends on the presence of a 5′ overlapping sequence and an embedded inverted SINEB2 element. These features are shared by other natural Antisense transcripts and can confer regulatory activity to an artificial Antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as mTORC1 inhibition by rapamycin causes an increase in UCHL1 protein that is associated to the shuttling of Antisense Uchl1 RNA from the nucleus to the cytoplasm. Antisense Uchl1 RNA is then required for the association of the overlapping sense protein-coding mRNA to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.
