MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro

作者：Trivellin Giampaolo; Butz Henriett; Delhove Juliette; Igreja Susana; Chahal Harvinder S; Zivkovic Vladimir; McKay Tristan; Patocs Attila; Grossman Ashley B; Korbonits Marta^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2012, 303(6): E708-E719.

DOI：10.1152/ajpendo.00546.2011

• miR-107
• pituitary adenoma

Abnormal microRNA (miRNA) expression profiles have recently been associated with sporadic pituitary adenomas, suggesting that miRNAs can contribute to tumor formation; miRNAs are small noncoding RNAs that inhibit posttranscriptional expression of target mRNAs by binding to target sequences usually located in the 3%26apos;-UTR. In this study, we investigated the role played by miR-107, a miRNA associated with different human cancers, in sporadic pituitary adenomas and its interaction with the pituitary tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP). miR-107 expression was evaluated in pituitary adenoma and normal pituitary samples using microRNA screen TLDA (TaqMan Low-Density Array) and RT-qPCR assays. We show that miR-107 expression was significantly upregulated in GH-secreting and nonfunctioning pituitary adenomas. We found that human AIP-3%26apos;-UTR is a target of miR-107 since miR-107 inhibited in vitro AIP expression to 53.9 +/- 2% of the miRNA control in a luciferase assay and reduced endogenous AIP mRNA expression to 53 +/- 22% of the miRNA control in human cells. However, we did not observe a negative correlation between AIP and miR-107 expression in the human tumor samples. Furthermore, we show that miR-107 overexpression inhibited cell proliferation in human neuroblastoma and rat pituitary adenoma cells. In conclusion, miR-107 is overexpressed in pituitary adenomas and may act as a tumor suppressor. We have identified and confirmed AIP as a miR-107 target gene. Expression data in human samples suggest that the expression of AIP and miR-107 could be influenced by a combination of tumorigenic factors as well as compensatory mechanisms stimulated by the tumorigenic process.

• 出版日期2012-9