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Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer

Treatment of chemo-resistant ovarian cancer (OvCa) remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. Here we report that multiple mechanisms that promote OvCa progression and chemo-resistance could be inhibited by ectopic expression of miR-15a and...

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Autores principales: Dhar Dwivedi, Shailendra Kumar, Mustafi, Soumyajit Banerjee, Mangala, Lingegowda S., Jiang, Dahai, Pradeep, Sunila, Rodriguez-Aguayo, Cristian, Ling, Hui, Ivan, Cristina, Mukherjee, Priyabrata, Calin, George A., Lopez-Berestein, Gabriel, Sood, Anil K., Bhattacharya, Resham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924772/
https://www.ncbi.nlm.nih.gov/pubmed/26918603
http://dx.doi.org/10.18632/oncotarget.7618
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author Dhar Dwivedi, Shailendra Kumar
Mustafi, Soumyajit Banerjee
Mangala, Lingegowda S.
Jiang, Dahai
Pradeep, Sunila
Rodriguez-Aguayo, Cristian
Ling, Hui
Ivan, Cristina
Mukherjee, Priyabrata
Calin, George A.
Lopez-Berestein, Gabriel
Sood, Anil K.
Bhattacharya, Resham
author_facet Dhar Dwivedi, Shailendra Kumar
Mustafi, Soumyajit Banerjee
Mangala, Lingegowda S.
Jiang, Dahai
Pradeep, Sunila
Rodriguez-Aguayo, Cristian
Ling, Hui
Ivan, Cristina
Mukherjee, Priyabrata
Calin, George A.
Lopez-Berestein, Gabriel
Sood, Anil K.
Bhattacharya, Resham
author_sort Dhar Dwivedi, Shailendra Kumar
collection PubMed
description Treatment of chemo-resistant ovarian cancer (OvCa) remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. Here we report that multiple mechanisms that promote OvCa progression and chemo-resistance could be inhibited by ectopic expression of miR-15a and miR-16. Significant correlations between low expression of miR-16, high expression of BMI1 and shortened overall survival (OS) were noted in high grade serous (HGS) OvCa patients upon analysis of The Cancer Genome Atlas (TCGA). Targeting BMI1, in vitro with either microRNA reduced clonal growth of OvCa cells. Additionally, epithelial to mesenchymal transition (EMT) as well as expression of the cisplatin transporter ATP7B were inhibited by miR-15a and miR-16 resulting in decreased degradation of the extra-cellular matrix and enhanced sensitization of OvCa cells to cisplatin. Nanoliposomal delivery of the miR-15a and miR-16 combination, in a pre-clinical chemo-resistant orthotopic mouse model of OvCa, demonstrated striking reduction in tumor burden compared to cisplatin alone. Thus, with the advent of miR replacement therapy some of which are in Phase 2 clinical trials, miR-15a and miR-16 represent novel ammunition in the anti-OvCa arsenal.
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spelling pubmed-49247722016-07-13 Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer Dhar Dwivedi, Shailendra Kumar Mustafi, Soumyajit Banerjee Mangala, Lingegowda S. Jiang, Dahai Pradeep, Sunila Rodriguez-Aguayo, Cristian Ling, Hui Ivan, Cristina Mukherjee, Priyabrata Calin, George A. Lopez-Berestein, Gabriel Sood, Anil K. Bhattacharya, Resham Oncotarget Research Paper Treatment of chemo-resistant ovarian cancer (OvCa) remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. Here we report that multiple mechanisms that promote OvCa progression and chemo-resistance could be inhibited by ectopic expression of miR-15a and miR-16. Significant correlations between low expression of miR-16, high expression of BMI1 and shortened overall survival (OS) were noted in high grade serous (HGS) OvCa patients upon analysis of The Cancer Genome Atlas (TCGA). Targeting BMI1, in vitro with either microRNA reduced clonal growth of OvCa cells. Additionally, epithelial to mesenchymal transition (EMT) as well as expression of the cisplatin transporter ATP7B were inhibited by miR-15a and miR-16 resulting in decreased degradation of the extra-cellular matrix and enhanced sensitization of OvCa cells to cisplatin. Nanoliposomal delivery of the miR-15a and miR-16 combination, in a pre-clinical chemo-resistant orthotopic mouse model of OvCa, demonstrated striking reduction in tumor burden compared to cisplatin alone. Thus, with the advent of miR replacement therapy some of which are in Phase 2 clinical trials, miR-15a and miR-16 represent novel ammunition in the anti-OvCa arsenal. Impact Journals LLC 2016-02-23 /pmc/articles/PMC4924772/ /pubmed/26918603 http://dx.doi.org/10.18632/oncotarget.7618 Text en Copyright: © 2016 Dhar Dwivedi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Dhar Dwivedi, Shailendra Kumar
Mustafi, Soumyajit Banerjee
Mangala, Lingegowda S.
Jiang, Dahai
Pradeep, Sunila
Rodriguez-Aguayo, Cristian
Ling, Hui
Ivan, Cristina
Mukherjee, Priyabrata
Calin, George A.
Lopez-Berestein, Gabriel
Sood, Anil K.
Bhattacharya, Resham
Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer
title Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer
title_full Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer
title_fullStr Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer
title_full_unstemmed Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer
title_short Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer
title_sort therapeutic evaluation of microrna-15a and microrna-16 in ovarian cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924772/
https://www.ncbi.nlm.nih.gov/pubmed/26918603
http://dx.doi.org/10.18632/oncotarget.7618
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