PMID- 28469779 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 9 IP - 4 DP - 2017 TI - Analysis of differentially expressed microRNAs in MEN1 parathyroid adenomas. PG - 1743-1753 AB - Multiple Endocrine Neoplasia type 1 (MEN1) syndrome is a rare complex tumor-predisposing hereditary disorder, inherited in an autosomal dominant manner (OMIM 131100). MEN1 is characterized by tumors of the parathyroids, the neuroendocrine cells of the gastro-entero-pancreatic tract, and the anterior pituitary. The molecular mechanisms that control parathyroid tumorigenesis are still poorly understood. Here we studied the global microRNAs (miRNAs) expression profile in MEN1 parathyroid adenomas to understand the role of these regulatory factors in MEN1 parathyroid tumorigenesis. miRNA arrays containing 1890 human miRNAs were used to profile seven different MEN1 parathyroid adenomas (four presenting somatic loss of heterozygosity (LOH) at 11q13 and three still retaining one wild type copy of the MEN1 gene). Eight miRNAs in non-LOH MEN1 parathyroid adenomas and two miRNAs in LOH MEN1 parathyroid adenomas resulted to be differentially expressed, with a significant fold change, with respect to the control pool. Six microRNAs also resulted to be differentially expressed between LOH MEN1 parathyroid adenomas and non-LOH MEN1 parathyroid adenomas. Significantly differentially expressed miRNAs were all validated by SYBR green real-time quantitative RT-PCR. Pearson correlation coefficient indicated miR-4258, miR-664 and miR-1301 as the most significant miRNAs. In silico target-prediction and network analysis showed miR-664 and miR-1301 as organized in predicted GRNs with genes interested in parathyroid adenomas and carcinomas. In conclusion, our study identified three new miRNAs involved in the MEN1 parathyroid neoplasia, directly targeting genes associated with the development of different inheritable forms of parathyroid tumors. These identified miRNAs could be revealed as prognostic and diagnostic biomarkers for parathyroid tumors to improve the diagnosis of MEN1 neoplasia and other syndromes. FAU - Luzi, Ettore AU - Luzi E AD - Unit of Bone and Mineral Metabolic Diseases, Department of Surgery and Translational Medicine, University of FlorenceFlorence, Italy. FAU - Ciuffi, Simone AU - Ciuffi S AD - Unit of Bone and Mineral Metabolic Diseases, Department of Surgery and Translational Medicine, University of FlorenceFlorence, Italy. FAU - Marini, Francesca AU - Marini F AD - Unit of Bone and Mineral Metabolic Diseases, Department of Surgery and Translational Medicine, University of FlorenceFlorence, Italy. FAU - Mavilia, Carmelo AU - Mavilia C AD - Unit of Bone and Mineral Metabolic Diseases, Department of Surgery and Translational Medicine, University of FlorenceFlorence, Italy. FAU - Galli, Gianna AU - Galli G AD - Unit of Bone and Mineral Metabolic Diseases, Department of Surgery and Translational Medicine, University of FlorenceFlorence, Italy. FAU - Brandi, Maria Luisa AU - Brandi ML AD - Unit of Bone and Mineral Metabolic Diseases, Department of Surgery and Translational Medicine, University of FlorenceFlorence, Italy. LA - eng PT - Journal Article DEP - 20170415 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC5411922 OTO - NOTNLM OT - MEN1 OT - diagnostic biomarkers OT - gene regulatory networks OT - microRNAs OT - neoplasia OT - parathyroid adenomas OT - primary hyperparathyroidism COIS- None. EDAT- 2017/05/05 06:00 MHDA- 2017/05/05 06:01 PMCR- 2017/04/15 CRDT- 2017/05/05 06:00 PHST- 2016/10/04 00:00 [received] PHST- 2017/02/09 00:00 [accepted] PHST- 2017/05/05 06:00 [entrez] PHST- 2017/05/05 06:00 [pubmed] PHST- 2017/05/05 06:01 [medline] PHST- 2017/04/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2017 Apr 15;9(4):1743-1753. eCollection 2017.