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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Metastasis | Research article

Aberrantly expressed miR-188-5p promotes gastric cancer metastasis by activating Wnt/β-catenin signaling

Authors: Yun Li, Xiaoli Yan, Jiajian Shi, Yun He, Jie Xu, Liying Lin, Wannan Chen, Xinjian Lin, Xu Lin

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Gastric cancer (GC) is one of the most common human cancers with the high rate of recurrence, metastasis and mortality. Aberrantly expressed microRNAs (miRNAs) are associated with invasion and metastasis in various human cancers. Recently, miR-188-5p has been indicated as an oncogene in GC since it promotes GC cell growth and metastasis. However, the underlying molecular mechanism remains to be fully defined.

Methods

Using Significance Analysis of Microarrays (SAM) screening, we identified that miR-188-5p is associated with overall survival and lymph node metastasis in patients with GC. The functional impact of miR-188-5p on GC metastasis was validated using in vitro and in vivo assays. The regulatory function of miR-188-5p on Wnt/β-catenin signaling activation through directly targeting PTEN was proven using quantitative real-time PCR, western blot analysis, a dual-luciferase assay, a Transwell assay, and immunofluorescence. Immunohistochemical analyses further confirmed the clinical significance of miR-188-5p in GC.

Results

MiR-188-5p diminishes tumor suppressor PTEN expression, and further increases phospho-Ser9 of GSK3β to activate Wnt/β-catenin signaling in GC. Consequently, miR-188-5p enhanced the migration and invasion of GC cells in vitro and tumor metastasis in vivo, whereas inhibition of miR-188-5p had the opposite effects. Moreover, miR-188-5p was negatively correlated with PTEN expression but positively correlated with nuclear β-catenin staining in GC samples.

Conclusions

Our findings revealed a model of the miR-188-5p-PTEN-β-catenin axis in GC, which mediates the constitutive activation of Wnt/β-catenin signaling and promotes tumor metastasis, inferring that miR-188-5p is a potential therapeutic target to treat GC.
Appendix
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Metadata
Title
Aberrantly expressed miR-188-5p promotes gastric cancer metastasis by activating Wnt/β-catenin signaling
Authors
Yun Li
Xiaoli Yan
Jiajian Shi
Yun He
Jie Xu
Liying Lin
Wannan Chen
Xinjian Lin
Xu Lin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5731-0

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