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Oncogenic miR-9 is a target of erlotinib in NSCLCs

EGFR-targeted cancer therapy is a breakthrough in non-small cell carcinoma. miRNAs have been proved to play important roles in cancer. Currently, for the role of miRNAs in EGFR-targeted cancer therapy is unclear. In this study, first we found that erlotinib reduced the expression of miR-9. MiR-9 exp...

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Detalles Bibliográficos
Autores principales: Chen, Xi, Zhu, Lingjun, Ma, Zhuo, Sun, Geng, Luo, Xuan, Li, Min, Zhai, Sulan, Li, Ping, Wang, Xuerong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655475/
https://www.ncbi.nlm.nih.gov/pubmed/26593208
http://dx.doi.org/10.1038/srep17031
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author Chen, Xi
Zhu, Lingjun
Ma, Zhuo
Sun, Geng
Luo, Xuan
Li, Min
Zhai, Sulan
Li, Ping
Wang, Xuerong
author_facet Chen, Xi
Zhu, Lingjun
Ma, Zhuo
Sun, Geng
Luo, Xuan
Li, Min
Zhai, Sulan
Li, Ping
Wang, Xuerong
author_sort Chen, Xi
collection PubMed
description EGFR-targeted cancer therapy is a breakthrough in non-small cell carcinoma. miRNAs have been proved to play important roles in cancer. Currently, for the role of miRNAs in EGFR-targeted cancer therapy is unclear. In this study, first we found that erlotinib reduced the expression of miR-9. MiR-9 expression was increased in human lung cancer tissues compared with peripheral normal tissues, and miR-9 promoted the growth of NSCLC cells. Overexpression of miR-9 decreased the growth inhibitory effect of erlotinib. Second, miR-9 decreased FoxO1 expression by directly inhibition of its mRNA translation. Adenovirus-mediated overexpression of FoxO1 or siRNA-mediated downregulation of FoxO1 negatively regulated cell growth. And exogenous overexpression FoxO1 reduced the pro-growth effect of miR-9. Finally, we found that erlotinib upregulated FoxO1 protein expression. Moreover, overexpression of miR-9 decreased erlotinib-induced FoxO1 expression, and overexpression of FoxO1 enhanced the growth inhibitory effects of erlotinib. Additionally, we found that erlotinib downregulates miR-9 expression through suppressing the transcrption of miR-9-1 and enhanced DNA methylation maybe involved. These findings suggest that oncogenic miR-9 targeted FoxO1 to promote cell growth, and downregulation of this axis was involved in erlotinib’s growth inhibitory effects. Clarifying the regulation of miRNAs by erlotinib may indicate novel strategies for enhancing EGFR-targeted cancer therapy.
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spelling pubmed-46554752015-11-27 Oncogenic miR-9 is a target of erlotinib in NSCLCs Chen, Xi Zhu, Lingjun Ma, Zhuo Sun, Geng Luo, Xuan Li, Min Zhai, Sulan Li, Ping Wang, Xuerong Sci Rep Article EGFR-targeted cancer therapy is a breakthrough in non-small cell carcinoma. miRNAs have been proved to play important roles in cancer. Currently, for the role of miRNAs in EGFR-targeted cancer therapy is unclear. In this study, first we found that erlotinib reduced the expression of miR-9. MiR-9 expression was increased in human lung cancer tissues compared with peripheral normal tissues, and miR-9 promoted the growth of NSCLC cells. Overexpression of miR-9 decreased the growth inhibitory effect of erlotinib. Second, miR-9 decreased FoxO1 expression by directly inhibition of its mRNA translation. Adenovirus-mediated overexpression of FoxO1 or siRNA-mediated downregulation of FoxO1 negatively regulated cell growth. And exogenous overexpression FoxO1 reduced the pro-growth effect of miR-9. Finally, we found that erlotinib upregulated FoxO1 protein expression. Moreover, overexpression of miR-9 decreased erlotinib-induced FoxO1 expression, and overexpression of FoxO1 enhanced the growth inhibitory effects of erlotinib. Additionally, we found that erlotinib downregulates miR-9 expression through suppressing the transcrption of miR-9-1 and enhanced DNA methylation maybe involved. These findings suggest that oncogenic miR-9 targeted FoxO1 to promote cell growth, and downregulation of this axis was involved in erlotinib’s growth inhibitory effects. Clarifying the regulation of miRNAs by erlotinib may indicate novel strategies for enhancing EGFR-targeted cancer therapy. Nature Publishing Group 2015-11-23 /pmc/articles/PMC4655475/ /pubmed/26593208 http://dx.doi.org/10.1038/srep17031 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Xi
Zhu, Lingjun
Ma, Zhuo
Sun, Geng
Luo, Xuan
Li, Min
Zhai, Sulan
Li, Ping
Wang, Xuerong
Oncogenic miR-9 is a target of erlotinib in NSCLCs
title Oncogenic miR-9 is a target of erlotinib in NSCLCs
title_full Oncogenic miR-9 is a target of erlotinib in NSCLCs
title_fullStr Oncogenic miR-9 is a target of erlotinib in NSCLCs
title_full_unstemmed Oncogenic miR-9 is a target of erlotinib in NSCLCs
title_short Oncogenic miR-9 is a target of erlotinib in NSCLCs
title_sort oncogenic mir-9 is a target of erlotinib in nsclcs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655475/
https://www.ncbi.nlm.nih.gov/pubmed/26593208
http://dx.doi.org/10.1038/srep17031
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