Introduction: MicroRNAs (miRs) are 1629 nucleotide long, non-coding RNA molecules that post-transcriptionally regulate gene expression via RNA interference. It has been shown that they participate in control of cell proliferation, cell differentiation, signal transduction, cell death and carcinogenesis.
Aim: To examine the role of the miRs in sporadic pituitary tumourigenesis.
Methods: Twenty-five sporadic pituitary adenoma specimens were analyzed approved by the Ethical Committee of the Hungarian Health Council. Real time quantitative PCR using microRNA low density array (TLDA) with in silico target prediction were used for identification of miRs potentially involved in pituitary tumourigenesis.
Results: Expression profile revealed 87 differentially expressed miRs: 17 miRs only in the normal pituitary tissues, 4 only in adenomas and 66 with a difference more than 2.5-fold between normal and adenoma tissues. Examining the miRs chromosomal localizations we found that the 87 differentially expressed miRs were located in 51 chromosomal regions. In the underexpressed group a cluster of 18 miRs was banded to 14q32.31, 4 miRs to Xq37.3, and 8 miRs to Xp11.22 region. Combining these results with the in silico target prediction we selected six miRs for further validation using Taqman assays. MiR-17-5p, miR-107, miR-221, miR-98, miR-225 and miR-429 were overexpressed in 88, 80, 68, 76, 56 and 60% of adenoma tissues, respectively. MiR-17-5p potentially targets PRKAR1A while miR-107 AIP.
Conclusions: The genes of the downregulated miRs map to regions which have already been identified as a hotspot for loss of heterozygosity in several tumours suggesting that in these regions a potential tumour suppressor gene which has not been identified yet is located or, based on our results, miRs located here could function as a tumour suppressor. miR-17-5p and miR-107 through regulation of the expression of the PRKAR1A and AIP may contribute to the pathogenesis of sporadic pituitary tumours.
25 - 29 Apr 2009
European Society of Endocrinology