RESUMEN
BACKGROUND: The present study is aimed at exploring the specific expression of miR-193a-3p and the mechanism underlying miR-193a-3p-mediated mesenchymal transition (MT), invasion, and migration in glioma. METHODS: The gene expression profile datasets of GSE39486 and GSE25676 were downloaded from the National Center for Biotechnology (NCBI). Data regarding the expression of miR-193a-3p and survival curves were derived from Chinese Glioma Genome Atlas (CGGA). Online websites including miRWalk, DIANA, and starbase were employed to predict the target genes for miR-193a-3p. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the Omicsbean online software. Module analysis of the protein-protein interaction (PPI) networks was performed by the plug-in Molecular Complex Detection (MCODE), and the degrees of genes were calculated by CytoHubba plug-in of Cytoscape. Survival curves were based on the Gene Expression Profile Interaction Analysis (GEPIA). Transwell, wound healing, and Western blot experiments were performed to investigate the effects of miR-193a-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) on the invasion, migration, and MT of glioma. RESULTS: miR-193a-3p was highly expressed in glioma tissues and significantly correlated with poor survival in patients with glioma. The target genes for miR-193a-3p were involved in many cancer-related signaling pathways. The PPI showed 11 genes with both high degrees and MCODE scores in the network. Survival analysis demonstrated that the expression of BTRC was significantly correlated with the prognosis of patients with glioma. The results from the transwell, wound healing, and Western blot analyses suggested that miR-193a-3p promoted the invasion, migration, and MT of glioma cells, which could be reversed by BTRC. CONCLUSIONS: miR-193a-3p was upregulated in patients with glioma and could affect the invasion, migration, and MT of glioma by regulating BTRC.
Asunto(s)
Neoplasias Encefálicas , Transición Epitelial-Mesenquimal/genética , Glioma , MicroARNs , Proteínas con Repetición de beta-Transducina , Encéfalo/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Glioma/genética , Glioma/metabolismo , Glioma/mortalidad , Glioma/patología , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica/genética , Pronóstico , Mapas de Interacción de Proteínas/genética , Transcriptoma/genética , Proteínas con Repetición de beta-Transducina/genética , Proteínas con Repetición de beta-Transducina/metabolismoRESUMEN
In order to prove whether downregulation of COX-2 (Cyclooxygenase-2) could modulate the epithelial- mesenchymal transition (EMT) of breast cancer, celecoxib and siRNA were respectively used to inhibit COX-2 function and expression in MDA-MB-231 cells. The EMT reversal effect in the RNAi treated group was better than that of the celecoxib group while there were no obvious differences in the medium PGE2 levels between the two groups. The results show that COX-2 pathways may contribute considerably to EMT of breast cancer cells, partially dependent on the PGE2 cascade. Akt2, ZEB2 and Snail were measured to clarify the underlying mechanisms of COX-2 on EMT; COX-2 may modulate EMT of breast cancer by regulating these factors. This finding may be helpful to elucidate the mechanisms of selective COX-2 inhibitor action in EMT modulation in breast cancer.