PMID- 27098433 OWN - NLM STAT- MEDLINE DCOM- 20170724 LR - 20171205 IS - 1742-2051 (Electronic) IS - 1742-2051 (Linking) VI - 12 IP - 6 DP - 2016 May 24 TI - An autoregulatory network between menin and pri-miR-24-1 is required for the processing of its specific modulator miR-24-1 in BON1 cells. PG - 1922-8 LID - 10.1039/c6mb00118a [doi] AB - Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary cancer complex syndrome manifesting a variety of endocrine and non-endocrine neoplasms and lesions. MEN1 is characterized by tumours of the parathyroids, of the neuroendocrine cells of the gastroenteropancreatic tract, and of the anterior pituitary. The MEN1 gene, a tumour suppressor gene, encodes the menin protein. Loss of heterozygosity (LOH) at 11q13 is typical of MEN1 tumours in agreement with Knudson's two-hit hypothesis. We previously showed that the MEN1 parathyroid tumorigenesis is under the control of an "incoherent feedback loop" between miR-24-1 and the menin protein that generates a "Gene Regulatory Network" (GRN) 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. Here we show, in the BON1 cell line derived from lymphnode metastasis of a human carcinoid tumour of the pancreas, that menin binds specifically to the primary RNA sequence pri-miR-24-1 by promoting the miR-24-1 biogenesis. Network simulation showed a new feed-forward loop between menin, microRNA-24-1 and Musashi-1 proteins. This result shows a novel mechanism whereby menin, a RNA-binding protein, facilitates the processing of its specific miRNA by regulating the dynamics of the menin-miR-24 Gene Regulatory Network at the level of pri-miRNA processing. FAU - Luzi, Ettore AU - Luzi E AD - Department of Surgery and Translational Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. eluzi@unifi.it francesca.marini@dmsc.unifi.it simone.ciuffi@unifi.it gianna.galli@unifi.it marialuisa.brandi@unifi.it. FAU - Marini, Francesca AU - Marini F AD - Department of Surgery and Translational Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. eluzi@unifi.it francesca.marini@dmsc.unifi.it simone.ciuffi@unifi.it gianna.galli@unifi.it marialuisa.brandi@unifi.it. FAU - Ciuffi, Simone AU - Ciuffi S AD - Department of Surgery and Translational Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. eluzi@unifi.it francesca.marini@dmsc.unifi.it simone.ciuffi@unifi.it gianna.galli@unifi.it marialuisa.brandi@unifi.it. FAU - Galli, Gianna AU - Galli G AD - Department of Surgery and Translational Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. eluzi@unifi.it francesca.marini@dmsc.unifi.it simone.ciuffi@unifi.it gianna.galli@unifi.it marialuisa.brandi@unifi.it. FAU - Brandi, Maria Luisa AU - Brandi ML AD - Department of Surgery and Translational Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. eluzi@unifi.it francesca.marini@dmsc.unifi.it simone.ciuffi@unifi.it gianna.galli@unifi.it marialuisa.brandi@unifi.it. LA - eng PT - Journal Article PL - England TA - Mol Biosyst JT - Molecular bioSystems JID - 101251620 RN - 0 (MEN1 protein, human) RN - 0 (MIRN24 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Transcription Factors) SB - IM MH - Cell Line, Tumor MH - Chromosomes, Human, Pair 11 MH - *Gene Expression Regulation MH - Humans MH - MicroRNAs/*genetics MH - Microsatellite Repeats MH - Mutation MH - Protein Binding MH - Proto-Oncogene Proteins/*metabolism MH - RNA Processing, Post-Transcriptional MH - Transcription Factors/metabolism EDAT- 2016/04/22 06:00 MHDA- 2017/07/25 06:00 CRDT- 2016/04/22 06:00 PHST- 2016/04/22 06:00 [entrez] PHST- 2016/04/22 06:00 [pubmed] PHST- 2017/07/25 06:00 [medline] AID - 10.1039/c6mb00118a [doi] PST - ppublish SO - Mol Biosyst. 2016 May 24;12(6):1922-8. doi: 10.1039/c6mb00118a.