Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2020; 26(6): 627-644
Published online Feb 14, 2020. doi: 10.3748/wjg.v26.i6.627
MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells
Fu-Bing Yu, Juan Sheng, Jia-Man Yu, Jing-Hua Liu, Xiang-Xin Qin, Bo Mou
Fu-Bing Yu, Juan Sheng, Jing-Hua Liu, Department of Gastroenterology, The Fourth Affiliated Hospital of Kunming Medical University, Kunming 650021, Yunnan Province, China
Jia-Man Yu, Department of Clinical Laboratory, The Geriatrics Hospital of Yunnan Province, Kunming 650011, Yunnan Province, China
Xiang-Xin Qin, Bo Mou, Department of Clinical Nutrition, The Fourth Affiliated Hospital of Kunming Medical University, Kunming 650021, Yunnan Province, China
Author contributions: Sheng J designed the research; Yu FB performed the research; Yu JM and Mou B analyzed the data; Liu JH and Qin XX wrote the manuscript.
Institutional review board statement: This study was reviewed and approved by the Fourth Affiliated Hospital of Kunming Medical University Ethics Committee.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: The authors declare no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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. See:
Corresponding author: Bo Mou, MD, Chief Physician, Department of Clinical Nutrition, The Fourth Affiliated Hospital of Kunming Medical University, No.176, Qingnian Road, Wuhua District, Kunming 650021, Yunnan Province, China.
Received: October 10, 2019
Peer-review started: October 10, 2019
First decision: November 27, 2019
Revised: December 3, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: February 14, 2020

Colorectal cancer (CRC) is one of the most common malignancies worldwide.


To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms.


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.


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.


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.

Keywords: MiR-19a-3p, Forkhead box F2, Wnt/β-catenin signaling pathway, Biological function, Colorectal cancer, Western blot

Core tip: Colorectal cancer (CRC) has a high rate of mortality, and patients with this disease often miss the optimal treatment period due to the lack of clinical symptoms of early CRC, which affects their prognosis. At present, CRC is extremely difficult to prevent and treat. Therefore, this study investigated the changes in biological functions of CRC cells from the perspective of the CRC mechanism, with the goal of evaluating the effects of microRNA miR-19a-3p-mediated regulation of the Forkhead box F2-mediated Wnt/β-catenin signaling pathway on the biological functions of CRC cells.