Background: Abnormal microRNAs (miRNAs) expression profiles have been recently associated with sporadic pituitary adenomas, suggesting that miRNAs can contribute to tumor formation. miRNAs are small noncoding RNAs which inhibit post-transcriptional expression of target mRNAs by binding to complementary sequences usually located in the 3′ untranslated region (3′UTR). However, the substantial lack of knowledge about miRNAs targets hinder full understanding of the mechanisms by which they influence tumorigenesis.
Methods: The expression level of miR-107 were evaluated in 17 sporadic pituitary adenoma tissues and nine normal pituitary samples using a microRNA screen TLDA and qRT-PCR analyses. Pre-miR-107 and anti-miR-107 were used to examine the effects of miR-107 expression on cell proliferation and colony formation in human SH-SY5Y and rat GH3 cells. A luciferase reporter assay was used to examine the in silico predicted target sites in the 3′UTR of the aryl hydrocarbon receptor interacting protein (AIP) gene.
Results: miR-107 expression was found significantly upregulated in pituitary adenoma tissues compared to normal pituitaries. Overexpression of miR-107 inhibited cell proliferation of both the rat and the human cell lines tested. Anti-miR-107 increased colony formation by 2.5 fold in human cells. We provide direct evidence that AIP−3′UTR is a functional target of miR-107 as miR-107 inhibits human AIP expression to 53.9±2% of the scrambled miRNA control in a luciferase expression model and it reduces endogenous AIP expression to 53±22% of the scrambled miRNA control in SH-SY5Y cells.
Conclusions: These results suggest that miR-107 functions as a tumor suppressor gene in neuroblastoma and pituitary adenoma cells and that it may play a role in pituitary adenoma pathogenesis.