miR‐363‐3p induces EMT via the Wnt/β‐catenin pathway in glioma cells by targeting CELF2

Abstract

In our previous study, we reported that CELF2 has a tumour‐suppressive function in glioma. Here, we performed additional experiments to elucidate better its role in cancer. The expression profile of CELF2 was analysed by the GEPIA database, and Kaplan–Meier curves were used to evaluate the overall survival rates. Four different online databases were used to predict miRNAs targeting CELF2, and the luciferase assay was performed to identify the binding site. The biological effects of miR‐363‐3p and CELF2 were also investigated in vitro using MTT, Transwell, and flow cytometry assays. Western blotting, qPCR, and TOP/FOP flash dual‐luciferase assays were performed to investigate the impact of miR‐363‐3p and CELF2 on epithelial‐to‐mesenchymal transition (EMT) and the Wnt/β‐catenin pathway. The effect of miR‐363‐3p was also tested in vivo using a xenograft mouse model. We observed an abnormal expression pattern of CELF2 in glioma cells, and higher CELF2 expression correlated with better prognosis. We identified miR‐363‐3p as an upstream regulator of CELF2 and confirmed its direct binding to the 3′‐untranslated region of CELF2. Cell function experiments showed that miR‐363‐3p affected multiple aspects of glioma cells. Suppressing miR‐363‐3p expression inhibited glioma cell proliferation and invasion, as well as promoted cell death via attenuating EMT and blocking the Wnt/β‐catenin pathway. These effects could be abolished by the downregulation of CELF2. Treatment with ASO‐miR‐363‐3p decreased tumour size and weight in nude mice. In conclusion, miR‐363‐3p induced the EMT, which resulted in increased migration and invasion and reduced apoptosis in glioma cell lines, via the Wnt/β‐catenin pathway by targeting CELF2.

The plasma miRNome and venous thromboembolism in high‐grade glioma: miRNA Sequencing of a nested case–control cohort

“…Interestingly, miR‐363‐3p was also found to be differentially regulated in patients with or without VTE in our study. Experimental studies showed that miR‐363‐3p supports glioma growth by inducing epithelial‐to‐mesenchymal transition, increasing migration and proliferation and reducing apoptosis 25 . Other miRNAs identified as predictors of VTE in the study by Oto et al could not be confirmed in our study cohort.…”

“…Experimental studies showed that miR-363-3p supports glioma growth by inducing epithelial-to-mesenchymal transition, increasing migration and proliferation and reducing apoptosis. 25 Other miRNAs identified as predictors of VTE in the study by While our mapping of potentially VTE-associated miRNAs of high-grade glioma patients was the main study goal, three further worthwhile contributions were generated during the course of the research. First, we here provide one of the largest and deepest miRNome datasets of peripheral blood of high-grade glioma patients-even without considering any reference to VTE and especially when considering that RNA sequencing was performed.…”

Novel cancer-fighting role of ticagrelor inhibits GTSE1-induced EMT by regulating PI3K/Akt/NF-κB signaling pathway in malignant glioma

“…When EMT is activated, E-cadherin expression decreases. In addition, the increase of N-cadherin and vimentin is also a key marker of the EMT process during tumor progression [ 32 ]. At present, EMT has been shown to occur in a variety of tumors, such as breast cancer, colorectal cancer and esophageal squamous cell carcinoma [ 33 , 34 ].…”

EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β‐catenin axis

“…EMX1 and WASF2 levels should be further explored as potential clinical metrics in SCG for patient stratification and disease prognostication. Considering that the other member of the EMX family of transcription factors, EMX2, has been proposed to as a potential suppressor of GBM cells (Falcone et al., 2016 ; Monnier et al., 2018 ), and the WNT/β‐catenin pathway has been report linking to the malignant phonotype of brain glioma (Fan et al., 2021 ; Xiang et al., 2022 ; Xu et al., 2019 ), the EMX1/WASF2/β‐catenin possibly also can be applied to gliomas occurring in other locations such as the brain. We would like to focus on this issue in the future researches.…”