MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Li, Tingting; Lai, Qiuhua; Wang, Shuyang; Cai, Juanjuan; Xiao, Zhiyuan; Deng, Danling; He, Liuqing; Jiao, Hongli; Ye, Yaping; Liang, Li; Ding, Yanqing; Liao, Wenting
• Is Part Of: Journal of experimental & clinical cancer research. Volume 35:Issue 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: miR-224 -- Proliferation -- Invasion -- Colorectal cancer -- Wnt/β-catenin -- GSK3β -- SFRP2; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s13046-016-0287-1
• Languages: English
• ISSNs: 1756-9966

Abstract

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.