Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1.

CONTEXT: MicroRNA (miRNA) are an important class of regulators of gene expression. Altered miRNA expression has been constantly found in human neoplasias and plays an important role in the process of carcinogenesis. OBJECTIVE: The aim of this study was to identify specific miRNA whose expression is altered in GH-secreting pituitary adenomas. DESIGN: Using a miRNACHIP microarray, we have analyzed the miRNA expression profile of human GH adenomas vs. normal pituitary gland. RESULTS: We report the identification of a set of miRNA, including miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, and miR-603, drastically and constantly down-regulated in GH adenomas. We demonstrate that these miRNA target genes such as high-mobility group A1 (HMGA1), HMGA2, and E2F1, whose overexpression and/or activation plays a critical role in pituitary tumorigenesis. We also show that the enforced expression of the down-regulated miRNA has a negative role on the growth regulation of pituitary adenoma cells. Finally, an inverse correlation is found between the expression of these miRNA and HMGA1 and HMGA2 protein levels in GH adenomas. CONCLUSION: Our study identifies a specific subset of miRNA, whose down-regulation might contribute to pituitary tumorigenesis.