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

Journal article

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'-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'-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.

Authors: Trivellin, G; Butz, H; Delhove, J; Igreja, S; Chahal, H

• Publication status: Published
• Journal: American journal of physiology. Endocrinology and metabolism
• Volume: 303
• Issue: 6
• Pages: E708-E719
• Publication date: 2012-09-01
• DOI: 10.1152/ajpendo.00546.2011
• EISSN: 1522-1555
• ISSN: 0193-1849
• Language: English
• Keywords: Pituitary Gland; Humans; Human Growth Hormone; Neuroblastoma; Oligonucleotide Array Sequence Analysis; Adenoma; Pituitary Neoplasms; Neoplasm Proteins; Rats; Gene Expression Regulation, Neoplastic; Intracellular Signaling Peptides and Proteins; Recombinant Proteins; MicroRNAs; Animals; Prolactin; Gene Expression Profiling; Up-Regulation; 3' Untranslated Regions; Mutant Proteins; RNA, Messenger; Cell Proliferation; Cell Line, Tumor