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

Am J Physiol Endocrinol Metab. 2012 Sep 15;303(6):E708-19. doi: 10.1152/ajpendo.00546.2011. Epub 2012 Jul 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenoma / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Human Growth Hormone / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • Intracellular Signaling Peptides and Proteins / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutant Proteins / antagonists & inhibitors
  • Mutant Proteins / biosynthesis
  • Mutant Proteins / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neuroblastoma / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Gland / metabolism
  • Pituitary Neoplasms / metabolism*
  • Prolactin / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • Intracellular Signaling Peptides and Proteins
  • MIRN107 microRNA, human
  • MicroRNAs
  • Mutant Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • aryl hydrocarbon receptor-interacting protein
  • Human Growth Hormone
  • Prolactin