Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy

Abstract Dysregulation of miRNA expression has been implicated in cancer. Numerous strategies have been explored to modulate miR but sub-optimal delivery and inability to concurrently target multiple pathways involved in tumor progression have limited their efficacy. In this study, we explored the p...

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Autores principales:	Deepak Bhere, Nahid Arghiani, Esther Revai Lechtich, Yizheng Yao, Sarah Alsaab, Fengfeng Bei, Maryam M. Matin, Khalid Shah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b320c564c7ac41faa451f7f557aa22c3
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spelling	oai:doaj.org-article:b320c564c7ac41faa451f7f557aa22c32021-12-02T14:06:51ZSimultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy10.1038/s41598-020-58072-w2045-2322https://doaj.org/article/b320c564c7ac41faa451f7f557aa22c32020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-58072-whttps://doaj.org/toc/2045-2322Abstract Dysregulation of miRNA expression has been implicated in cancer. Numerous strategies have been explored to modulate miR but sub-optimal delivery and inability to concurrently target multiple pathways involved in tumor progression have limited their efficacy. In this study, we explored the potential co-modulation of upregulated miR-21 and downregulated miR-7 to enhance therapeutic outcomes in heterogenic tumor types. We first engineered lentiviral (LV) and adeno-associated viral (AAV) vectors that preferentially express anti-sense miR against miR-21(miRzip-21) and show that modulating miR-21 via miRzip extensively targets tumor cell proliferation, migration and invasion in vitro in a broad spectrum of cancer types and has therapeutic efficacy in vivo. Next, we show a significantly increased expression of caspase-mediated apoptosis by simultaneously downregulating miR-21 and upregulating miR-7 in different tumor cells. In vivo co-treatment with AAV-miRzip-21 and AAV-miR-7 in mice bearing malignant brain tumors resulted in significantly decreased tumor burden with a corresponding increase in survival. To our knowledge, this is the first study that demonstrates the therapeutic efficacy of simultaneously upregulating miR-7 and downregulating miR-21 and establishes a roadmap towards clinical translation of modulating miRs for various cancer types.Deepak BhereNahid ArghianiEsther Revai LechtichYizheng YaoSarah AlsaabFengfeng BeiMaryam M. MatinKhalid ShahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deepak Bhere Nahid Arghiani Esther Revai Lechtich Yizheng Yao Sarah Alsaab Fengfeng Bei Maryam M. Matin Khalid Shah Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
description	Abstract Dysregulation of miRNA expression has been implicated in cancer. Numerous strategies have been explored to modulate miR but sub-optimal delivery and inability to concurrently target multiple pathways involved in tumor progression have limited their efficacy. In this study, we explored the potential co-modulation of upregulated miR-21 and downregulated miR-7 to enhance therapeutic outcomes in heterogenic tumor types. We first engineered lentiviral (LV) and adeno-associated viral (AAV) vectors that preferentially express anti-sense miR against miR-21(miRzip-21) and show that modulating miR-21 via miRzip extensively targets tumor cell proliferation, migration and invasion in vitro in a broad spectrum of cancer types and has therapeutic efficacy in vivo. Next, we show a significantly increased expression of caspase-mediated apoptosis by simultaneously downregulating miR-21 and upregulating miR-7 in different tumor cells. In vivo co-treatment with AAV-miRzip-21 and AAV-miR-7 in mice bearing malignant brain tumors resulted in significantly decreased tumor burden with a corresponding increase in survival. To our knowledge, this is the first study that demonstrates the therapeutic efficacy of simultaneously upregulating miR-7 and downregulating miR-21 and establishes a roadmap towards clinical translation of modulating miRs for various cancer types.
format	article
author	Deepak Bhere Nahid Arghiani Esther Revai Lechtich Yizheng Yao Sarah Alsaab Fengfeng Bei Maryam M. Matin Khalid Shah
author_facet	Deepak Bhere Nahid Arghiani Esther Revai Lechtich Yizheng Yao Sarah Alsaab Fengfeng Bei Maryam M. Matin Khalid Shah
author_sort	Deepak Bhere
title	Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
title_short	Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
title_full	Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
title_fullStr	Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
title_full_unstemmed	Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
title_sort	simultaneous downregulation of mir-21 and upregulation of mir-7 has anti-tumor efficacy
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/b320c564c7ac41faa451f7f557aa22c3
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Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy

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