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Synthetic regulatory RNAs selectively suppress the progression of bladder cancer

The traditional treatment for cancer is lack of specificity and efficacy. Modular synthetic regulatory RNAs, such as inhibitive RNA (iRNA) and active RNA (aRNA), may overcome these limitations. Here, we synthesize a new iRNA to bind the upstream activating sequence (UAS) of a minimal promoter that d...

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Autores principales: Zhuang, Chengle, Huang, Xinbo, Zhuang, Changshui, Luo, Xiaomin, Zhang, Xiaowei, Cai, Zhiming, Gui, Yaoting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663129/
https://www.ncbi.nlm.nih.gov/pubmed/29084575
http://dx.doi.org/10.1186/s13046-017-0626-x
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author Zhuang, Chengle
Huang, Xinbo
Zhuang, Changshui
Luo, Xiaomin
Zhang, Xiaowei
Cai, Zhiming
Gui, Yaoting
author_facet Zhuang, Chengle
Huang, Xinbo
Zhuang, Changshui
Luo, Xiaomin
Zhang, Xiaowei
Cai, Zhiming
Gui, Yaoting
author_sort Zhuang, Chengle
collection PubMed
description The traditional treatment for cancer is lack of specificity and efficacy. Modular synthetic regulatory RNAs, such as inhibitive RNA (iRNA) and active RNA (aRNA), may overcome these limitations. Here, we synthesize a new iRNA to bind the upstream activating sequence (UAS) of a minimal promoter that drives expression of artificial miRNAs (amiRNAs) targeting MYC, which represses the binding interaction between UAS and GAL4 fusion protein (GAL4-VP64) in GAL4/UAS system. The aRNA driven by a tumor-specific mutant human telomerase reverse transcriptase (hTERT) promoter is created to interact with iRNA to expose UAS again in bladder cancer. Without the aRNA, mRNA and protein levels of MYC, cell growth, cell apoptosis and cell migration were no significance in two bladder cancer cell lines, T24 and 5637, and human foreskin fibroblast (HFF) cells. The aRNA significantly inhibited the expression of MYC in mRNA and protein levels, as well as the proliferation and migration of the cancer cells, but not in HFF cells. These results indicated that regulatory RNAs selectively controlled the expression of amiRNAs and ultimately suppress the progression of bladder cancer cells without affecting normal cells. Synthetic regulatory RNAs might be a selective therapeutic approach for bladder cancer.
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spelling pubmed-56631292017-11-01 Synthetic regulatory RNAs selectively suppress the progression of bladder cancer Zhuang, Chengle Huang, Xinbo Zhuang, Changshui Luo, Xiaomin Zhang, Xiaowei Cai, Zhiming Gui, Yaoting J Exp Clin Cancer Res Research The traditional treatment for cancer is lack of specificity and efficacy. Modular synthetic regulatory RNAs, such as inhibitive RNA (iRNA) and active RNA (aRNA), may overcome these limitations. Here, we synthesize a new iRNA to bind the upstream activating sequence (UAS) of a minimal promoter that drives expression of artificial miRNAs (amiRNAs) targeting MYC, which represses the binding interaction between UAS and GAL4 fusion protein (GAL4-VP64) in GAL4/UAS system. The aRNA driven by a tumor-specific mutant human telomerase reverse transcriptase (hTERT) promoter is created to interact with iRNA to expose UAS again in bladder cancer. Without the aRNA, mRNA and protein levels of MYC, cell growth, cell apoptosis and cell migration were no significance in two bladder cancer cell lines, T24 and 5637, and human foreskin fibroblast (HFF) cells. The aRNA significantly inhibited the expression of MYC in mRNA and protein levels, as well as the proliferation and migration of the cancer cells, but not in HFF cells. These results indicated that regulatory RNAs selectively controlled the expression of amiRNAs and ultimately suppress the progression of bladder cancer cells without affecting normal cells. Synthetic regulatory RNAs might be a selective therapeutic approach for bladder cancer. BioMed Central 2017-10-30 /pmc/articles/PMC5663129/ /pubmed/29084575 http://dx.doi.org/10.1186/s13046-017-0626-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhuang, Chengle
Huang, Xinbo
Zhuang, Changshui
Luo, Xiaomin
Zhang, Xiaowei
Cai, Zhiming
Gui, Yaoting
Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
title Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
title_full Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
title_fullStr Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
title_full_unstemmed Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
title_short Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
title_sort synthetic regulatory rnas selectively suppress the progression of bladder cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663129/
https://www.ncbi.nlm.nih.gov/pubmed/29084575
http://dx.doi.org/10.1186/s13046-017-0626-x
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