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ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression

BACKGROUND: Currently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific...

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Autores principales: Ma, Ming-Hui, An, Jia-Xiang, Zhang, Cheng, Liu, Jie, Liang, Yu, Zhang, Chun-Dong, Zhang, Zhen, Dai, Dong-Qiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364449/
https://www.ncbi.nlm.nih.gov/pubmed/30774556
http://dx.doi.org/10.1186/s12935-019-0742-0
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author Ma, Ming-Hui
An, Jia-Xiang
Zhang, Cheng
Liu, Jie
Liang, Yu
Zhang, Chun-Dong
Zhang, Zhen
Dai, Dong-Qiu
author_facet Ma, Ming-Hui
An, Jia-Xiang
Zhang, Cheng
Liu, Jie
Liang, Yu
Zhang, Chun-Dong
Zhang, Zhen
Dai, Dong-Qiu
author_sort Ma, Ming-Hui
collection PubMed
description BACKGROUND: Currently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific miRNAs to form regulatory networks and facilitate the growth of gastric cancer (GC). METHODS: MiRNAs interacting with ZEB1-AS1 were screened for and selected by bioinformatics analysis. Overexpression or repression of ZEB1-AS1 was performed to determine whether it could regulate selected miRNAs. Quantitative real-time polymerase chain reactions (qPCR) validated the expression profiles of ZEB1-AS1 and miR-149-3p in GC cell lines and tissue. Statistical analysis determined the clinical significance of ZEB1-AS1 in relation to miR-149-3p. Cell counting, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. A luciferase reporter assay was utilized to confirm the putative miR-149-3p-binding sites in ZEB1-AS1. RESULTS: Briefly, bioinformatics analysis inferred that ZEB1-AS1 interacts with miR-204, miR-610, and miR-149. Gain- or loss-of function assays suggested that ZEB1-AS1 negatively regulates miR-149-3p, miR-204-5p and miR-610 in GC cells. Validated by qPCR, ZEB1-AS1 was up-regulated and miR-149-3p down-regulated in GC cells and tissue. Data analyses indicated that ZEB1-AS1 and miR-149-3p are associated with the independent diagnosis and prognosis of GC. Functional assays support the theory that miR-149-3p hinders GC proliferation, migration and invasion, whereas its overexpression abrogates the corresponding effects induced by ZEB1-AS1. Lastly, dissection of the molecular mechanisms involved indicated that ZEB1-AS1 can regulate GC partly via a ZEB1-AS1/miR-149-3p axis. CONCLUSIONS: ZEB1-AS1 can interact with specific miRNAs, forming a miRNA-mediated ceRNA network and promoting GC progress, partly through a ZEB1-AS1/miR-149-3p axis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0742-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-63644492019-02-15 ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression Ma, Ming-Hui An, Jia-Xiang Zhang, Cheng Liu, Jie Liang, Yu Zhang, Chun-Dong Zhang, Zhen Dai, Dong-Qiu Cancer Cell Int Primary Research BACKGROUND: Currently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific miRNAs to form regulatory networks and facilitate the growth of gastric cancer (GC). METHODS: MiRNAs interacting with ZEB1-AS1 were screened for and selected by bioinformatics analysis. Overexpression or repression of ZEB1-AS1 was performed to determine whether it could regulate selected miRNAs. Quantitative real-time polymerase chain reactions (qPCR) validated the expression profiles of ZEB1-AS1 and miR-149-3p in GC cell lines and tissue. Statistical analysis determined the clinical significance of ZEB1-AS1 in relation to miR-149-3p. Cell counting, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. A luciferase reporter assay was utilized to confirm the putative miR-149-3p-binding sites in ZEB1-AS1. RESULTS: Briefly, bioinformatics analysis inferred that ZEB1-AS1 interacts with miR-204, miR-610, and miR-149. Gain- or loss-of function assays suggested that ZEB1-AS1 negatively regulates miR-149-3p, miR-204-5p and miR-610 in GC cells. Validated by qPCR, ZEB1-AS1 was up-regulated and miR-149-3p down-regulated in GC cells and tissue. Data analyses indicated that ZEB1-AS1 and miR-149-3p are associated with the independent diagnosis and prognosis of GC. Functional assays support the theory that miR-149-3p hinders GC proliferation, migration and invasion, whereas its overexpression abrogates the corresponding effects induced by ZEB1-AS1. Lastly, dissection of the molecular mechanisms involved indicated that ZEB1-AS1 can regulate GC partly via a ZEB1-AS1/miR-149-3p axis. CONCLUSIONS: ZEB1-AS1 can interact with specific miRNAs, forming a miRNA-mediated ceRNA network and promoting GC progress, partly through a ZEB1-AS1/miR-149-3p axis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0742-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-06 /pmc/articles/PMC6364449/ /pubmed/30774556 http://dx.doi.org/10.1186/s12935-019-0742-0 Text en © The Author(s) 2019 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 Primary Research
Ma, Ming-Hui
An, Jia-Xiang
Zhang, Cheng
Liu, Jie
Liang, Yu
Zhang, Chun-Dong
Zhang, Zhen
Dai, Dong-Qiu
ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
title ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
title_full ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
title_fullStr ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
title_full_unstemmed ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
title_short ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
title_sort zeb1-as1 initiates a mirna-mediated cerna network to facilitate gastric cancer progression
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364449/
https://www.ncbi.nlm.nih.gov/pubmed/30774556
http://dx.doi.org/10.1186/s12935-019-0742-0
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