Dataset Information

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

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/?-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 GSK3? to activate Wnt/?-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 ?-catenin staining in GC samples.

Conclusions

Our findings revealed a model of the miR-188-5p-PTEN-?-catenin axis in GC, which mediates the constitutive activation of Wnt/?-catenin signaling and promotes tumor metastasis, inferring that miR-188-5p is a potential therapeutic target to treat GC.

SUBMITTER: Li Y

PROVIDER: S-EPMC6537442 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

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

Li Yun Y Yan Xiaoli X Shi Jiajian J He Yun Y Xu Jie J Lin Liying L Chen Wannan W Lin Xinjian X Lin Xu X

BMC cancer 20190528 1

<h4>Background</h4>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.<h4>Methods</h4>Using Significance Analysis of Microarrays (SAM) scre ...[more]

PMID: 31138169

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