1Center for Hereditary Endocrine Tumors, 2DeGene Spin-off, University of Florence, Medical School of Florence, Florence, Italy.
Background: Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by the occurrence of tumors of the parathyroids, ofthe neuroendocrine cells of the gastroentero-pancreatic tract, and ofthe anterior pituitary. MEN 1 gene, a tumor suppressor gene, encodes menin protein. Loss of heterozygosity (LOH) at 11q13 is typical of MEN1 tumors. Other associations found in MEN1 patients include foregut carcinoids, facial angiofibromas, lipomas, collagenomas, meningiomas, and smooth muscle cell tumors. MicroRNA genes encode a large, highly conserved family of small, non-coding RNAs which negatively regulate expression of specific target genes. The miR-15a-miR-16a cluster is located on chromosome 13q14, a region frequently deleted in parathyroid cancer and other tumor types, and specific evidence supports the involvement of this microRNA cluster in human tumorogenesis.
Aim: We therefore hypothesized that alteration of miR-15amiR16a, may contribute to parathyroid tumorigenesis. Materials and Methods: We sought to test this hypothesis by assessing loss of heterozygosity (LOH) at 13q14 and 11 q13 loci in sporadic and MEN1-associated parathyroid adenomas and, by Northern blot and qRT-PCR analysis, the expression profiles of miR-15a, miR-16a and MEN1 mRNA.
Results and Conclusions: the expression of both miR-15 and miR-16 resulted to be differentially regulated between MEN1 and sporadic adenomas thus indicating a possible role of these microRNAs as "oncomirs".