RESUMEN
Colorectal cancer (CRC) is among the most common gastrointestinal malignancies worldwide. eIF3a is highly expressed in a variety of cancer types, yet its role in CRC remains unclear. We introduced ectopic eIF3a expression in CRC cells to investigate its relevance to various malignant behaviors. Further, we silenced eIF3a to explore its effect on tumor growth in a nude mouse tumor xenograft model. Finally, the molecular mechanisms through which eIF3a regulates malignancy in CRC cells were explored through bioinformatics analysis combined with the use of a specific PI3K inhibitor (LY294002). eIF3a was highly expressed in the peripheral blood and cancer tissue of CRC patients. Malignancy and tumor growth were significantly inhibited by silencing eIF3a, while overexpression promoted malignant behaviors, with a positive correlation between PI3K/AKT activation and eIF3a expression. Taken together, eIF3a plays an oncogenic role in CRC by regulating PI3K/AKT signaling and is a potential biomarker for CRC diagnosis and prognostic monitoring.
Asunto(s)
Neoplasias Colorrectales , Factor 3 de Iniciación Eucariótica , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Factor 3 de Iniciación Eucariótica/metabolismo , Factor 3 de Iniciación Eucariótica/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Desnudos , Línea Celular Tumoral , Proliferación Celular , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Masculino , Regulación Neoplásica de la Expresión GénicaRESUMEN
The exostosin (EXT) protein family is involved in diverse human diseases. However, the expression and prognostic value of EXT genes in human lung squamous cell carcinoma (LUSC) is not well understood. In this study, we analyzed the association between expression of EXT1 and EXT2 genes and survival in patients with LUSC using bioinformatics resources such as Oncomine and The Cancer Genome Atlas (TCGA) databases, the Gene Expression Profiling Interactive Analysis (GEPIA) server and Kaplan-Meier plotter. Furthermore, regulatory microRNAs (miRNAs) were predicted for EXT1 and used to establish a potential miRNA-messenger RNA (mRNA) regulation network for LUSC using the ENCORI platform. We observed that EXT1 and EXT2 expression levels were higher in LUSC than those in normal tissues. However, only EXT1 expression was significantly associated with poor overall survival (OS) in LUSC patients. Functional annotation enrichment analysis showed that genes co-expressed with the EXT1 gene were enriched in biological processes such as cell adhesion and migration, and KEGG pathways such as extracellular matrix receptor interactions, complement and coagulation cascades, and cell death. Furthermore, three miRNAs, hsa-mir-190a-5p, hsa-mir-195-5p, and hsa-mir-490-3p, were identified to be potentially involved in the regulation of EXT1. In summary, we identified EXT1 expression as a novel potential prognostic marker for human LUSC and the regulatory miRNAs that could possibly contribute to the prognosis of the disease.
