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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Main Authors:	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
Format:	Online
Language:	English
Published:	Impact Journals LLC 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924772/

id	pubmed-4924772
recordtype	oai_dc
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 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
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
spellingShingle	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
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
title	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_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_sort	therapeutic evaluation of microrna-15a and microrna-16 in ovarian cancer
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.
publisher	Impact Journals LLC
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924772/
_version_	1613600935254163456

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

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