title: The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the Men1 tumorigenesis by mimicking the "Knudson's second hit".
abstract: Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare hereditary cancer disorder characterized by tumors of the parathyroids, of the neuroendocrine cells, of the gastro-entero-pancreatic tract, of the anterior pituitary, and by non-endocrine neoplasms and lesions. MEN1 gene, a tumor suppressor gene, encodes menin protein. Loss of heterozygosity at 11q13 is typical of MEN1 tumors, in agreement with the Knudson's two-hit hypothesis. In silico analysis with Target Scan, Miranda and Pictar-Vert softwares for the prediction of miRNA targets indicated miR-24-1 as capable to bind to the 3'UTR of MEN1 mRNA. We investigated this possibility by analysis of miR-24-1 expression profiles in parathyroid adenomatous tissues from MEN1 gene mutation carriers, in their sporadic non-MEN1 counterparts, and in normal parathyroid tissue. Interestingly, the MEN1 tumorigenesis seems to be under the control of a "negative feedback loop" between miR-24-1 and menin protein, that mimics the second hit of Knudson's hypothesis and that could buffer the effect of the stochastic factors that contribute to the onset and progression of this disease. Our data show an alternative way to MEN1 tumorigenesis and, probably, to the "two-hit dogma". The functional significance of this regulatory mechanism in MEN1 tumorigenesis is also the basis for opening future developments of RNA antagomir(s)-based strategies in the in vivo control of tumorigenesis in MEN1 carriers.
authors: Metabolic Bone Unit, Department of Internal Medicine, University of Florence, Florence, Italy.
authors: Ettore
authors: E
authors: Luzi
authors: Francesca
authors: F
authors: Marini
authors: Francesca
authors: F
authors: Giusti
authors: Gianna
authors: G
authors: Galli
authors: Loredana
authors: L
authors: Cavalli
authors: Maria Luisa
authors: ML
authors: Brandi
mesh_terms: D020413:3' Untranslated Regions; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D025461:Feedback, Physiological; D020869:Gene Expression Profiling; D019656:Loss of Heterozygosity; D035683:MicroRNAs / Q000502:physiology*; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C105373:MEN1 protein, human; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins