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miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2

Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significa...

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Detalles Bibliográficos
Autores principales: Zhang, Liang, Huang, Ping, Li, Qing, Wang, Dong, Xu, Cheng-Xiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838973/
https://www.ncbi.nlm.nih.gov/pubmed/31689617
http://dx.doi.org/10.1016/j.omtn.2019.09.025
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author Zhang, Liang
Huang, Ping
Li, Qing
Wang, Dong
Xu, Cheng-Xiong
author_facet Zhang, Liang
Huang, Ping
Li, Qing
Wang, Dong
Xu, Cheng-Xiong
author_sort Zhang, Liang
collection PubMed
description Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy.
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spelling pubmed-68389732019-11-12 miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2 Zhang, Liang Huang, Ping Li, Qing Wang, Dong Xu, Cheng-Xiong Mol Ther Nucleic Acids Article Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy. American Society of Gene & Cell Therapy 2019-10-03 /pmc/articles/PMC6838973/ /pubmed/31689617 http://dx.doi.org/10.1016/j.omtn.2019.09.025 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhang, Liang
Huang, Ping
Li, Qing
Wang, Dong
Xu, Cheng-Xiong
miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2
title miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2
title_full miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2
title_fullStr miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2
title_full_unstemmed miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2
title_short miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2
title_sort mir-134-5p promotes stage i lung adenocarcinoma metastasis and chemoresistance by targeting dab2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838973/
https://www.ncbi.nlm.nih.gov/pubmed/31689617
http://dx.doi.org/10.1016/j.omtn.2019.09.025
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