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

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....

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Autores principales: Li, Tingting, Lai, Qiuhua, Wang, Shuyang, Cai, Juanjuan, Xiao, Zhiyuan, Deng, Danling, He, Liuqing, Jiao, Hongli, Ye, Yaping, Liang, Li, Ding, Yanqing, Liao, Wenting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731927/
https://www.ncbi.nlm.nih.gov/pubmed/26822534
http://dx.doi.org/10.1186/s13046-016-0287-1
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author Li, Tingting
Lai, Qiuhua
Wang, Shuyang
Cai, Juanjuan
Xiao, Zhiyuan
Deng, Danling
He, Liuqing
Jiao, Hongli
Ye, Yaping
Liang, Li
Ding, Yanqing
Liao, Wenting
author_facet Li, Tingting
Lai, Qiuhua
Wang, Shuyang
Cai, Juanjuan
Xiao, Zhiyuan
Deng, Danling
He, Liuqing
Jiao, Hongli
Ye, Yaping
Liang, Li
Ding, Yanqing
Liao, Wenting
author_sort Li, Tingting
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0287-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-47319272016-01-30 MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer Li, Tingting Lai, Qiuhua Wang, Shuyang Cai, Juanjuan Xiao, Zhiyuan Deng, Danling He, Liuqing Jiao, Hongli Ye, Yaping Liang, Li Ding, Yanqing Liao, Wenting J Exp Clin Cancer Res Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0287-1) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-29 /pmc/articles/PMC4731927/ /pubmed/26822534 http://dx.doi.org/10.1186/s13046-016-0287-1 Text en © Li et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Li, Tingting
Lai, Qiuhua
Wang, Shuyang
Cai, Juanjuan
Xiao, Zhiyuan
Deng, Danling
He, Liuqing
Jiao, Hongli
Ye, Yaping
Liang, Li
Ding, Yanqing
Liao, Wenting
MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
title MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
title_full MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
title_fullStr MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
title_full_unstemmed MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
title_short MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
title_sort microrna-224 sustains wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731927/
https://www.ncbi.nlm.nih.gov/pubmed/26822534
http://dx.doi.org/10.1186/s13046-016-0287-1
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