MiR-1258/MEX3A Axis Inhibits the Proliferation of Thyroid Cancer Cells and EMT by Inhibiting the AKT Pathway

Abstract

Objective: Thyroid cancer (TC) is a malignant tumor. The incidence of this disease has increased progressively yearly, seriously threatening the lives safety of Chinese residents. The aim of this study was using the Cancer Genome Atlas (TCGA) database, combined with the means of bioinformatics, to screen the candidate gene targets that affect the occurrence, prognosis and survival of TC, and verify the influence of candidate genes on the phenotype of TC through experiments, so as to supply a basis for the search for new TC treatment targets. Methods: Differential micro-ribonucleic acids (miRNAs) and messenger-ribonucleic acids (mRNAs) associated with TC were obtained from the TCGA database and analyzed using bioinformatics. The target gene of microRNA (miR)-1258 was verified, through a double luciferase assay. The proliferation, migration and invasion capability of TC cells were detected through 5-ethynyl-2-deoxyuridine (EDU) staining and the Transwell experiment. The expressions of miR-1258, Mex-3 RNA binding family member A (MEX3A), protein kinase B (AKT), Vimentin, E-Cadherin and Snail in TC cells and animal models were tested through quantitative polymerase chain reaction (qPCR) and Western blot. In animal models, hematoxylin-eosin (HE) staining was applied to observe the pathological conditions of tumor tissues, and TdT-mediated dUTP nick end labeling (TUNEL) was used to detect apoptosis. Results: This project proved that MEX3A was the target gene of miRNA and miR-1258 could inhibit its expression. Overexpression of miR-1258 could significantly decrease the propagation, migration and invasion ability of TC cells, inhibit tumor growth in TC animal models and improve the pathological conditions of tumor tissues. After miR-1258 and MEX3A were overexpressed simultaneously, the proliferation, migration and invasion of TC cells were weaker than the overexpression of MEX3A alone (p < 0.05). MiR-1258 increased E-Cadherin and reduced Vimentin, Snail and AKT’s phosphorylation form (p-AKT) expression through targeted inhibition of MEX3A. Conclusions: MiR-1258 suppressed the AKT pathway through targeted inhibition of MEX3A, thereby inhibiting the proliferation and epithelial-mesenchymal transition (EMT) of TC cells.