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MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. AIM: To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms. METHODS: Sixty-two CRC patients admitted to the hospital were enrolled into the st...

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Autores principales: Yu, Fu-Bing, Sheng, Juan, Yu, Jia-Man, Liu, Jing-Hua, Qin, Xiang-Xin, Mou, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029353/
https://www.ncbi.nlm.nih.gov/pubmed/32103872
http://dx.doi.org/10.3748/wjg.v26.i6.627
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author Yu, Fu-Bing
Sheng, Juan
Yu, Jia-Man
Liu, Jing-Hua
Qin, Xiang-Xin
Mou, Bo
author_facet Yu, Fu-Bing
Sheng, Juan
Yu, Jia-Man
Liu, Jing-Hua
Qin, Xiang-Xin
Mou, Bo
author_sort Yu, Fu-Bing
collection PubMed
description BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. AIM: To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms. METHODS: Sixty-two CRC patients admitted to the hospital were enrolled into the study group, and sixty healthy people from the same period were assigned to the control group. Elbow venous blood was sampled from the patients and healthy individuals, and blood serum was saved for later analysis. MiR-19a-3p mimics, miR-19a-3p inhibitor, miR-negative control, small interfering-FOXF2, and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells. Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells, and western blot (WB) analysis was conducted to evaluate the levels of FOXF2, glycogen synthase kinase 3 beta (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), β-catenin, p-β-catenin, α-catenin, N-cadherin, E-cadherin, and vimentin. The MTT, Transwell, and wound healing assays were applied to analyze cell proliferation, invasion, and migration, respectively, and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2. RESULTS: The patients showed high serum levels of miR-19a-3p and low levels of FOXF2, and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8. MiR-19a-3p and FOXF2 were related to sex, tumor size, age, tumor-node-metastasis staging, lymph node metastasis, and differentiation of CRC patients. Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelial-mesenchymal transition, invasion, migration, and proliferation of cells. WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3β, β-catenin, N-cadherin, and vimentin; and increased the levels of GSK-3β, p-β-catenin, α-catenin, and E-cadherin. The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2. In addition, a rescue experiment revealed that there were no differences in cell proliferation, invasion, and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group. CONCLUSION: Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/β-catenin signaling pathway, thereby affecting the epithelial-mesenchymal transition, proliferation, invasion, and migration of cells. Thus, miR-19a-3p is likely to be a therapeutic target in CRC.
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spelling pubmed-70293532020-02-26 MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells Yu, Fu-Bing Sheng, Juan Yu, Jia-Man Liu, Jing-Hua Qin, Xiang-Xin Mou, Bo World J Gastroenterol Case Control Study BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. AIM: To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms. METHODS: Sixty-two CRC patients admitted to the hospital were enrolled into the study group, and sixty healthy people from the same period were assigned to the control group. Elbow venous blood was sampled from the patients and healthy individuals, and blood serum was saved for later analysis. MiR-19a-3p mimics, miR-19a-3p inhibitor, miR-negative control, small interfering-FOXF2, and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells. Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells, and western blot (WB) analysis was conducted to evaluate the levels of FOXF2, glycogen synthase kinase 3 beta (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), β-catenin, p-β-catenin, α-catenin, N-cadherin, E-cadherin, and vimentin. The MTT, Transwell, and wound healing assays were applied to analyze cell proliferation, invasion, and migration, respectively, and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2. RESULTS: The patients showed high serum levels of miR-19a-3p and low levels of FOXF2, and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8. MiR-19a-3p and FOXF2 were related to sex, tumor size, age, tumor-node-metastasis staging, lymph node metastasis, and differentiation of CRC patients. Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelial-mesenchymal transition, invasion, migration, and proliferation of cells. WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3β, β-catenin, N-cadherin, and vimentin; and increased the levels of GSK-3β, p-β-catenin, α-catenin, and E-cadherin. The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2. In addition, a rescue experiment revealed that there were no differences in cell proliferation, invasion, and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group. CONCLUSION: Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/β-catenin signaling pathway, thereby affecting the epithelial-mesenchymal transition, proliferation, invasion, and migration of cells. Thus, miR-19a-3p is likely to be a therapeutic target in CRC. Baishideng Publishing Group Inc 2020-02-14 2020-02-14 /pmc/articles/PMC7029353/ /pubmed/32103872 http://dx.doi.org/10.3748/wjg.v26.i6.627 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Case Control Study
Yu, Fu-Bing
Sheng, Juan
Yu, Jia-Man
Liu, Jing-Hua
Qin, Xiang-Xin
Mou, Bo
MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
title MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
title_full MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
title_fullStr MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
title_full_unstemmed MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
title_short MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
title_sort mir-19a-3p regulates the forkhead box f2-mediated wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
topic Case Control Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029353/
https://www.ncbi.nlm.nih.gov/pubmed/32103872
http://dx.doi.org/10.3748/wjg.v26.i6.627
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