Development of biomarkers for detecting the invasiveness of GH secreting pituitary adenoma

Abstract

MicroRNAs (miRNAs) have been implicated in the pathogenesis of many human tumors. miRNAs act not only as a tumor suppressor but also as an oncogene in some malignancies, including thyroid cancer, prostate cancer, and pancreatic cancer. However, few studies have been reported about the role of miRNAs on pituitary adenoma. It was hypothesized that miRNAs might be involved in tumor size and invasiveness of growth hormone (GH) secreting pituitary adenoma. miRNA for microarray was extracted and purified from 6 GH secreting pituitary adenoma patients. Three of them had the pituitary adenoma of Hardy classification I (non-invasive) and the others had the one of Hardy classification IV (invasive). The significance of data from microarray was re-evaluated with in-vitro condition using rat GH-producing cell (GH3) line before and after estradiol (E2) treatment. There was significant difference in expression profile of miRNA according to the invasiveness of pituitary adenoma. miRNA-338 and miRNA-652 was significantly up-regulated but miRNA-432 was significantly down-regulated in invasive pituitary adenoma. Several candidate transcripts from microarray were further explored with GH3 cell line. The most strongly differentially expressed miRNA was miRNA-338. In E2 treated GH3 cell, the expression of miRNA-338 increased as rising concentration of E2 treatment. p27 expression in GH3 was down-regulated after miRNA-338 inhibitor treatment. These data suggest that specific miRNA, especially miRNA-338 might influence on the progression of GH secreting pituitary adenoma