MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells.
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.
Yu FB
，Sheng J
，Yu JM
，Liu JH
，Qin XX
，Mou B
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MicroRNA-149 suppresses colorectal cancer cell migration and invasion by directly targeting forkhead box transcription factor FOXM1.
The aim of this study is to investigate the clinicopathological and prognostic values of miR-149 expression and its roles in colorectal cancer (CRC) progression.
qRT-PCR was performed to detect miR-149 expression in CRC cell lines or tissues. Also, the clinical significance of miR-149 expression was investigated. The study further explored whether miR-149 inhibits migration and invasion of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1).
miR-149 was significantly downregulated in CRC tissues, and low miR-149 expression was observed to be significantly correlated with lymph node or distant metastasis and advanced TNM stage of CRC patients. Patients with low miR-149 expression showed poorer prognosis than those with high miR-149 expression, and multivariate analyses indicated that status of miR-149 expression might be an independent prognostic factor. Gain- and loss - of - function assays indicated that miR-149 significantly inhibited growth, migration and invasion of CRC cells by targeting FOXM1. Furthermore, FOXM1 was significantly uiregulated in CRC tissues and inversely correlated with miR-149 expression.
mR-149 was an independent prognostic factor and could inhibit migration and invasion of CRC cells, at least partially by targeting FOXM1.
Xu K
，Liu X
，Mao X
，Xue L
，Wang R
，Chen L
，Chu X
... -
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