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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
- 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.
- Subjects
MICRORNA; COLON cancer; GENE expression; CELL proliferation; LUCIFERASES
- Publication
Journal of Experimental & Clinical Cancer Research (17569966), 2016, Vol 35, p1
- ISSN
1756-9966
- Publication type
Article
- DOI
10.1186/s13046-016-0287-1