MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro.
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.
Dept. of Endocrinology, Barts & The London School of Medicine, Queen Mary University of London, London, UK EC1M 6BQ.
Giampaolo
G
Trivellin
Henriett
H
Butz
Juliette
J
Delhove
Susana
S
Igreja
Harvinder S
HS
Chahal
Vladimir
V
Zivkovic
Tristan
T
McKay
Attila
A
Patócs
Ashley B
AB
Grossman
Márta
M
Korbonits
D020413:3' Untranslated Regions; D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation
D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D019382:Human Growth Hormone; D011388:Prolactin