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Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

BACKGROUND: The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated....

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Autores principales: Chen, Junjie, Gao, Shenmeng, Wang, Chunjing, Wang, Zhonggai, Zhang, Huxiang, Huang, Kate, Zhou, Bin, Li, Haiying, Yu, Zhijie, Wu, Jianbo, Chen, Chengshui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100283/
https://www.ncbi.nlm.nih.gov/pubmed/27821145
http://dx.doi.org/10.1186/s13046-016-0450-8
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author Chen, Junjie
Gao, Shenmeng
Wang, Chunjing
Wang, Zhonggai
Zhang, Huxiang
Huang, Kate
Zhou, Bin
Li, Haiying
Yu, Zhijie
Wu, Jianbo
Chen, Chengshui
author_facet Chen, Junjie
Gao, Shenmeng
Wang, Chunjing
Wang, Zhonggai
Zhang, Huxiang
Huang, Kate
Zhou, Bin
Li, Haiying
Yu, Zhijie
Wu, Jianbo
Chen, Chengshui
author_sort Chen, Junjie
collection PubMed
description BACKGROUND: The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated. METHODS: The expressions of miR-193a (miR-193a-5p) in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively. RESULTS: The expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice. CONCLUSION: Collectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0450-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-51002832016-11-08 Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers Chen, Junjie Gao, Shenmeng Wang, Chunjing Wang, Zhonggai Zhang, Huxiang Huang, Kate Zhou, Bin Li, Haiying Yu, Zhijie Wu, Jianbo Chen, Chengshui J Exp Clin Cancer Res Research BACKGROUND: The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated. METHODS: The expressions of miR-193a (miR-193a-5p) in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively. RESULTS: The expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice. CONCLUSION: Collectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0450-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-07 /pmc/articles/PMC5100283/ /pubmed/27821145 http://dx.doi.org/10.1186/s13046-016-0450-8 Text en © The Author(s). 2016 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
Chen, Junjie
Gao, Shenmeng
Wang, Chunjing
Wang, Zhonggai
Zhang, Huxiang
Huang, Kate
Zhou, Bin
Li, Haiying
Yu, Zhijie
Wu, Jianbo
Chen, Chengshui
Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
title Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
title_full Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
title_fullStr Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
title_full_unstemmed Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
title_short Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
title_sort pathologically decreased expression of mir-193a contributes to metastasis by targeting wt1-e-cadherin axis in non-small cell lung cancers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100283/
https://www.ncbi.nlm.nih.gov/pubmed/27821145
http://dx.doi.org/10.1186/s13046-016-0450-8
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