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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2016 | Research

MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer

Authors: Tingting Li, Qiuhua Lai, Shuyang Wang, Juanjuan Cai, Zhiyuan Xiao, Danling Deng, Liuqing He, Hongli Jiao, Yaping Ye, Li Liang, Yanqing Ding, Wenting Liao

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

Abstract

Background

Growing evidence suggests that Wnt/β-catenin pathway plays an important role in CRC development, progression and metastasis. Aberrant miR-224 expression has been reported in CRC. However, the mechanism of miR-224 promotes both proliferation and metastatic ability largely remains unclear.

Methods

Real-time PCR was used to quantify miR-224 expression. Luciferase reporter assays were conducted to confirm the activity of Wnt/β-catenin pathway and target gene associations, and immunofluorescence staining assay was performed to observe the nuclear translocation of β-catenin. Bioinformatics analysis combined with in vivo and vitro functional assays showed the potential target genes, GSK3β and SFRP2, of miR-224. Specimens from forty patients with CRC were analyzed for the expression of miR-224 and the relationship with GSK3β/SFRP2 by real-time PCR and western blot.

Results

Bioinformatics and cell luciferase function studies verified the direct regulation of miR-224 on the 3’-UTR of the GSK3β and SFRP2 genes, which leads to the activation of Wnt/β-catenin signaling and the nuclear translocation of β-catenin. In addition, knockdown of miR-224 significantly recovered the expression of GSK3β and SFRP2 and attenuated Wnt/β-catenin-mediated cell metastasis and proliferation. The ectopic upregulation of miR-224 dramatically inhibited the expression of GSK3β/SFRP2 and enhanced CRC proliferation and invasion.

Conclusion

Our research showed mechanistic links between miR-224 and Wnt/β-catenin in the pathogenesis of CRC through modulation of GSK3β and SFRP2.

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Title: MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
Authors: Tingting Li
Qiuhua Lai
Shuyang Wang
Juanjuan Cai
Zhiyuan Xiao
Danling Deng
Liuqing He
Hongli Jiao
Yaping Ye
Li Liang
Yanqing Ding
Wenting Liao
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-016-0287-1

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