Next-generation sequencing of microRNAs reveals a unique expression pattern in different types of pituitary adenomas

Abstract

Pituitary adenomas (PAs) are considered the most common intracranial tumor to cause serious morbidity because of dysregulated pituitary hormone secretions. Aberrant expression of microRNAs (miRNAs) is correlated with the development and function of the pituitary gland as well as the tumorigenesis of hypothalamic-pituitary axis-related pituitary tumors. In this study, we showed the differential expression patterns of miRNAs in NFPAs (nonfunctioning pituitary adenomas), GHPAs (growth hormone-secreting pituitary adenomas) and PRLPAs (prolactin-secreting pituitary adenomas) compared to those in three normal pituitary glands using the HiSeq 2000 sequencing system (Illumina). We validated miRNA expression using real-time quantitative polymerase chain reaction (RT-qPCR) analyses of samples from 73 patients (13 GHPAs, 42 NFPAs, and 18 PRLPAs) and 6 normal pituitary gland. We observed that miR-34c-3p was significantly downregulated in our PRLPA samples (p < 0.01), along with miR-34b-5p, miR-378 and miR-338-5p (all p < 0.05). In NFPAs, miR-493-5p was downregulated, and miR-181b-5p was significantly upregulated (p < 0.01). In GHPAs, miR-184 was significantly upregulated (p < 0.05). We observed that the tumor suppressive miR-124-3p was downregulated in both NFPAs and GHPAs. Taken together, we showed distinctive miRNA expression patterns in these three PAs, and these miRNA signatures in PA may have therapeutic potential as novel biomarkers for each type of PA.