MicroRNA expression in ACTH-producing pituitary tumors: up-regulation of microRNA-122 and-493 in pituitary carcinomas

MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis, and can function as tumor suppressor genes or oncogenes. The expression of miRNAs in pituitary carcinomas has not been previously examined. We used miRNA profiling with 1,145 probes to study miRNA expression in normal anterior pituitary (6 cases), adrenocorticotropin (ACTH)-producing adenomas (8 cases), and ACTH-producing pituitary carcinomas (two cases). Real-time RT-PCR and in situ hybridization were used to confirm and independently validate miRNAs that were significantly up-regulated or down-regulated between the pituitary tissues. There were more miRNAs up- (188) or down-regulated (160) between adenomas and normal pituitaries compared to carcinomas and normal pituitaries (92 up- and 91 down-regulated) or between carcinomas and adenomas (46 up- and 52 down-regulated). Both real-time RT-PCR and in situ hybridization showed significant up-regulation of miRNA-122 between pituitary carcinomas and adenomas. MiRNA-493 was also up-regulated in carcinomas compared to ACTH adenomas. Analysis of genes that miRNA-493 interacts with included LGALS3 and RUNX2 (http://microrna.sanger.ac.uk) both of which have been shown to have roles in pituitary tumor cell growth. These results provide information about marker miRNAs that may lead to further insights into the regulation of pituitary tumor growth and development.