miRNA-199a-5p functions as a tumor suppressor in prolactinomas

Abstract

AbstractProlactinomas are the most frequently observed pituitary adenomas (PAs), and 5%–18% tumors were resistant to the dopamine agonists (DAs). MicroRNAs (miRNAs) dysfunction play a key role in tumorigenesis. Agilent miRNA and an expression chip were used for six prolactinomas and three normal pituitary specimens. Differentially expressed genes were confirmed by RT-qPCR. The level of DDR1 and SAT1 was determined with tissue micro-array (TMA) and western blot. A MMQ cell line was used for functional experiments. We have identified 5-miRNA and 12 target gene signatures of prolactinomas through gene ontology analysis. miRNA-199a-5p was selected for experiments that integrated the results from prolactinomas specimens and a rat prolactinoma model induced by 17-b-estradiol. Tumors with low miRNA-199a-5p had a significantly invasive behavior and a higher tumor volume (p<0.05). DDR1 and SAT1, target genes of miRNA-199a-5p, had higher H-scores in the invasive group than those of the non-invasive group through TMA. An overexpression of miRNA-119a-5p suppressed the PRL secretion and the cell viability through upregulated the apoptosis level in MMQ cells (p<0.01). Furthermore, we found the target genes expression of DDR1 and SAT1 were affected by miRNA-199a-5p regardless of mRNA levels or protein levels. This study provided evidence that downregulation of miRNA-199a-5p may contribute to prolactinoma tumorigenesis.