Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers
Abstract Purpose: The oncogenic miR-155 is upregulated in many humancancers,anditsexpressionisincreasedinmoreaggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determ...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | inglés |
| Publicado: |
2016
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| Acceso en línea: | http://eprints.uanl.mx/18044/1/391.pdf |
| _version_ | 1824415109921898496 |
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| author | Van Roosbroeck, Katrien Fanini, Francesca Setoyama, Tetsuro Ivan, Cristina Rodríguez Aguayo, Cristian Fuentes Mattei, Enrique Xiao, Lianchun Vannini, Ivan Redis, Roxana S. D'Abundo, Lucilla Zhang, Xinna Nicoloso, Milena S. Rossi, Simona González Villasana, Vianey Rupaimoole, Rajesha Ferracin, Manuela Morabito, Fortunato Neri, Antonino Ruvolo, Peter P. Ruvolo, Vivian R. Pecot, Chad V. Amadori, Dino Abruzzo, Lynne V. Calin, Steliana Wang, Xuemei You, M. James Ferrajoli, Alessandra Orlowski, Robert Plunkett, William Lichtenberg, Tara M. Davuluri, Ramana V. Berindan Neagoe, Ioana Negrini, Massimo Wistuba, Ignacio I. Kantarjian, Hagop M. Sood, Anil K. Lopez Berestein, Gabriel Keating, Michael J. Fabbri, L. Muller Calin, George A. |
| author_facet | Van Roosbroeck, Katrien Fanini, Francesca Setoyama, Tetsuro Ivan, Cristina Rodríguez Aguayo, Cristian Fuentes Mattei, Enrique Xiao, Lianchun Vannini, Ivan Redis, Roxana S. D'Abundo, Lucilla Zhang, Xinna Nicoloso, Milena S. Rossi, Simona González Villasana, Vianey Rupaimoole, Rajesha Ferracin, Manuela Morabito, Fortunato Neri, Antonino Ruvolo, Peter P. Ruvolo, Vivian R. Pecot, Chad V. Amadori, Dino Abruzzo, Lynne V. Calin, Steliana Wang, Xuemei You, M. James Ferrajoli, Alessandra Orlowski, Robert Plunkett, William Lichtenberg, Tara M. Davuluri, Ramana V. Berindan Neagoe, Ioana Negrini, Massimo Wistuba, Ignacio I. Kantarjian, Hagop M. Sood, Anil K. Lopez Berestein, Gabriel Keating, Michael J. Fabbri, L. Muller Calin, George A. |
| author_sort | Van Roosbroeck, Katrien |
| collection | Repositorio Institucional |
| description | Abstract
Purpose: The oncogenic miR-155 is upregulated in many humancancers,anditsexpressionisincreasedinmoreaggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine theroleofmiR-155inresistancetochemotherapyandtoevaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expressionandthecombinationofmiR-155andTP53expression with cancer survival, we studied 956 patients with lung cancer,
chronic lymphocytic leukemia, and acute lymphoblastic leukemia. Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulationofmiR-155successfullyresensitizestumorstochemotherapy invivo.Weshowthatanti-miR-155-DOPCcanbeconsiderednontoxic in vivo. We further demonstrate that miR-155 and TP53 are linkedinanegativefeedbackmechanismandthatacombination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer. Conclusions: Our findings support the existence of an miR155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcomedrugresistance,animportantcauseofcancer-relateddeath. Clin Cancer Res; 23(11); 2891–904. �2016 AACR. |
| format | Article |
| id | eprints-18044 |
| institution | UANL |
| language | English |
| publishDate | 2016 |
| record_format | eprints |
| spelling | eprints-180442020-06-05T15:35:19Z http://eprints.uanl.mx/18044/ Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers Van Roosbroeck, Katrien Fanini, Francesca Setoyama, Tetsuro Ivan, Cristina Rodríguez Aguayo, Cristian Fuentes Mattei, Enrique Xiao, Lianchun Vannini, Ivan Redis, Roxana S. D'Abundo, Lucilla Zhang, Xinna Nicoloso, Milena S. Rossi, Simona González Villasana, Vianey Rupaimoole, Rajesha Ferracin, Manuela Morabito, Fortunato Neri, Antonino Ruvolo, Peter P. Ruvolo, Vivian R. Pecot, Chad V. Amadori, Dino Abruzzo, Lynne V. Calin, Steliana Wang, Xuemei You, M. James Ferrajoli, Alessandra Orlowski, Robert Plunkett, William Lichtenberg, Tara M. Davuluri, Ramana V. Berindan Neagoe, Ioana Negrini, Massimo Wistuba, Ignacio I. Kantarjian, Hagop M. Sood, Anil K. Lopez Berestein, Gabriel Keating, Michael J. Fabbri, L. Muller Calin, George A. Abstract Purpose: The oncogenic miR-155 is upregulated in many humancancers,anditsexpressionisincreasedinmoreaggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine theroleofmiR-155inresistancetochemotherapyandtoevaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expressionandthecombinationofmiR-155andTP53expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia. Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulationofmiR-155successfullyresensitizestumorstochemotherapy invivo.Weshowthatanti-miR-155-DOPCcanbeconsiderednontoxic in vivo. We further demonstrate that miR-155 and TP53 are linkedinanegativefeedbackmechanismandthatacombination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer. Conclusions: Our findings support the existence of an miR155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcomedrugresistance,animportantcauseofcancer-relateddeath. Clin Cancer Res; 23(11); 2891–904. �2016 AACR. 2016 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/18044/1/391.pdf http://eprints.uanl.mx/18044/1.haspreviewThumbnailVersion/391.pdf Van Roosbroeck, Katrien y Fanini, Francesca y Setoyama, Tetsuro y Ivan, Cristina y Rodríguez Aguayo, Cristian y Fuentes Mattei, Enrique y Xiao, Lianchun y Vannini, Ivan y Redis, Roxana S. y D'Abundo, Lucilla y Zhang, Xinna y Nicoloso, Milena S. y Rossi, Simona y González Villasana, Vianey y Rupaimoole, Rajesha y Ferracin, Manuela y Morabito, Fortunato y Neri, Antonino y Ruvolo, Peter P. y Ruvolo, Vivian R. y Pecot, Chad V. y Amadori, Dino y Abruzzo, Lynne V. y Calin, Steliana y Wang, Xuemei y You, M. James y Ferrajoli, Alessandra y Orlowski, Robert y Plunkett, William y Lichtenberg, Tara M. y Davuluri, Ramana V. y Berindan Neagoe, Ioana y Negrini, Massimo y Wistuba, Ignacio I. y Kantarjian, Hagop M. y Sood, Anil K. y Lopez Berestein, Gabriel y Keating, Michael J. y Fabbri, L. Muller y Calin, George A. (2016) Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers. Clinical Cancer Research, 23 (11). pp. 2891-2904. ISSN 1078-0432 http://doi.org/10.1158/1078-0432.CCR-16-1025 doi:10.1158/1078-0432.CCR-16-1025 |
| spellingShingle | Van Roosbroeck, Katrien Fanini, Francesca Setoyama, Tetsuro Ivan, Cristina Rodríguez Aguayo, Cristian Fuentes Mattei, Enrique Xiao, Lianchun Vannini, Ivan Redis, Roxana S. D'Abundo, Lucilla Zhang, Xinna Nicoloso, Milena S. Rossi, Simona González Villasana, Vianey Rupaimoole, Rajesha Ferracin, Manuela Morabito, Fortunato Neri, Antonino Ruvolo, Peter P. Ruvolo, Vivian R. Pecot, Chad V. Amadori, Dino Abruzzo, Lynne V. Calin, Steliana Wang, Xuemei You, M. James Ferrajoli, Alessandra Orlowski, Robert Plunkett, William Lichtenberg, Tara M. Davuluri, Ramana V. Berindan Neagoe, Ioana Negrini, Massimo Wistuba, Ignacio I. Kantarjian, Hagop M. Sood, Anil K. Lopez Berestein, Gabriel Keating, Michael J. Fabbri, L. Muller Calin, George A. Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers |
| title_full | Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers |
| title_fullStr | Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers |
| title_full_unstemmed | Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers |
| title_short | Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers |
| title_sort | combining anti mir 155 with chemotherapy for the treatment of lung cancers |
| url | http://eprints.uanl.mx/18044/1/391.pdf |
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