Scientific Reports, Volume (10), No (1), Year (2020-2)

Title : ( Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy )

Authors: Deepak Bhere , Nahid Arghiani , Esther Revai Lechtich , Yizheng Yao , Sarah Alsaab , Fengfeng Bei , Maryam Moghaddam Matin , Khalid Shah ,

Citation: BibTeX | EndNote

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.

Keywords

, Cancer therapy, Targeted therapies, miR-21, miR-7
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@article{paperid:1078924,
author = {Deepak Bhere and Arghiani, Nahid and Esther Revai Lechtich and Yizheng Yao and Sarah Alsaab and Fengfeng Bei and Moghaddam Matin, Maryam and Khalid Shah},
title = {Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy},
journal = {Scientific Reports},
year = {2020},
volume = {10},
number = {1},
month = {February},
issn = {2045-2322},
keywords = {Cancer therapy; Targeted therapies; miR-21; miR-7},
}

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%0 Journal Article
%T Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
%A Deepak Bhere
%A Arghiani, Nahid
%A Esther Revai Lechtich
%A Yizheng Yao
%A Sarah Alsaab
%A Fengfeng Bei
%A Moghaddam Matin, Maryam
%A Khalid Shah
%J Scientific Reports
%@ 2045-2322
%D 2020

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