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

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

Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial–mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1

Authors: Hui Miao, Nuan Wang, Lin-Xin Shi, Zheng Wang, Wen-Bo Song

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Accumulating evidence has highlighted the tumor suppressive roles of microRNA (miRNAs) in cervical cancer (CC). In the present study, we aim to delineate the functional relevance of microRNA-137 (miR-137) in influencing epithelial–mesenchymal transition (EMT), and other CC cell biological activities via the TGF-β/smad pathway by binding to GREM1.

Methods

Microarray analysis was initially adopted to predict the differentially expressed genes and the miRNAs related to CC, followed by the measurement of the expression patterns of GREM1, EMT-related factors in the CC tissues and the adjacent tissues. Dual luciferase reporter gene assay was conducted to determine the relationship between miR-137 and GREM1. Gain-of- and loss-of-function experiments were conducted to characterize the effects of miR-137 and GREM1 on the colony formation, proliferation, apoptosis, migration, and invasion of CC cells in vitro, and the tumorigenicity of the CC cells in nude mice. The TGF-β/smad pathway was subsequently blocked with si-TGF-β to investigate its involvement.

Results

Reduced miR-137 expression and increased GREM1 expression were predicted in CC, which was subsequently observed in the CC tissues and cells. Notably, GREM1 was a target gene of miR-137. The overexpressed miR-137 was found to inhibit EMT, cell proliferation, colony formation, invasion, migration and tumorigenesis in nude mice. In addition, miR-137 was noted to inhibit the activation of the TGF-β/smad pathway by binding to GREM1. The silencing of TGF-β1 was shown to reverse the effects induced by downregulated expression of miR-137.

Conclusions

This study suggests that upregulated miR-137 suppresses the tumor progression in CC via blocking the TGF-β/smad pathway by binding to and negatively regulating GREM1.
Appendix
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Metadata
Title
Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial–mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1
Authors
Hui Miao
Nuan Wang
Lin-Xin Shi
Zheng Wang
Wen-Bo Song
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/s12935-019-0852-8

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