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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Gastric Cancer | Primary research

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

Authors: Ming-Hui Ma, Jia-Xiang An, Cheng Zhang, Jie Liu, Yu Liang, Chun-Dong Zhang, Zhen Zhang, Dong-Qiu Dai

Published in: Cancer Cell International | Issue 1/2019

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Abstract

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.
Appendix
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Metadata
Title
ZEB1-AS1 initiates a miRNA-mediated ceRNA network to facilitate gastric cancer progression
Authors
Ming-Hui Ma
Jia-Xiang An
Cheng Zhang
Jie Liu
Yu Liang
Chun-Dong Zhang
Zhen Zhang
Dong-Qiu Dai
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0742-0

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