RESUMEN
Objective:To explore the biological functions of differentially expressed miRNAs and their target genes, and their regulatory relations in growth hormone (GH)-secreting pituitary adenoma.Methods:Four databases (miRDB, miRwalk, Targetscan7.2 and Starbase) were used to predict the target genes of differentially expressed miRNAs in GH-secreting pituitary adenoma, and GO, KEGG and protein-protein interaction network (PPI) analyses were performed on the target genes. Meaningful hub target genes were screened out and compared with mRNA sequencing results from the database; and then, a visual miRNA-target gene interaction network was constructed.Results:Totally, 113 up-regulated miRNAs target genes and 128 down-regulated miRNAs target genes were obtained with the protein interaction degree≥20. Further intersection was conducted to obtain 13 hub target genes; these genes were mainly involved in ubiquitin mediated proteolysis pathway. The regulatory miRNAs of the hub target genes were miR-15b, miR-365, miR-32-3p, and miR-486-5p.Conclusion:A miRNAs-hub target gene mutual regulation network closely related to GH-secreting pituitary adenoma is constructed with bioinformatics analysis tools, and some potential proteins and pathways related to the pathogenesis and pathological process of GH-secreting pituitary adenoma are discovered.
RESUMEN
Clinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs.