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: http://creativecommons.org/licenses/by-nc/4.0/
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. md3ue0mc@163.com
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
Processing time: 127 Days and 10.2 Hours
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

In this study, we studied the effects of regulating the Forkhead box F2 (FOXF2)-mediated Wnt/β-catenin signaling pathway by miR-19a-3p on the biological functions of CRC cells from the perspective of the mechanism of CRC, so as to explore the changes in biological functions of CRC cells.

Research objectives

This study evaluated the expression of miR-19a-3p and FOXF2 in patients with CRC and the relevant mechanisms.

Research methods

Elbow venous blood was sampled from CRC patients and healthy individuals, and blood serum was saved for later analysis. MiR-19a-3p-mimics, miR-19a-3p-inhibitor, miR-NC, si-FOXF2, and sh-FOXF2 were transfected into HT29 and HCT116 cells. Then quantitative polymerase chain reaction was applied to determine the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells, and Western blotting was conducted to determine the expression of FOXF2, 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 detect cell proliferation, invasion, and apoptosis, respectively, and the dual luciferase reporter assay was used to determine the relationship between miR-19a-3p and FOXF2.

Research results

MiR-19a-3p was highly expressed in the serum of the patients, while FOXF2 was lowly expressed in them. MiR-19a-3p and FOXF2 were related to age, sex, tumor size, tumor, node, metastasis staging, lymph node metastasis, and differentiation of patients with CRC. Silencing of miR-19a-3p and over-expression of FOXF2 suppressed epithelial-mesenchymal transition, proliferation, invasion, and migration of cells, and Western blot assay supported that silencing of miR-19a-3p and over-expression of FOXF2 significantly suppressed epithelial-mesenchymal transition. Dual luciferase reporter assay confirmed that there was a targeted relationship between miR-19a-3p and FOXF2. Therefore, inhibiting the expression of miR-19a-3p can affect the biological functions of CRC cells by promoting the expression of FOXF2.

Research conclusions

Inhibiting the expression of miR-19a-3p can affect the biological functions of CRC cells by promoting the expression of FOXF2.

Research perspectives

It has been confirmed that inhibiting the expression of miR-19a-3p can up-regulate the FOXF2-mediated Wnt/β-catenin signaling pathway, thus affecting the epithelial-mesenchymal transition, proliferation, invasion, and migration of cells, so miR-19a-3p is expected to be a potential therapeutic target for CRC.