PMID- 32780442 OWN - NLM STAT- MEDLINE DCOM- 20210728 LR - 20220531 IS - 1523-4681 (Electronic) IS - 0884-0431 (Linking) VI - 35 IP - 12 DP - 2020 Dec TI - The Oncosuppressors MEN1 and CDC73 Are Involved in lncRNA Deregulation in Human Parathyroid Tumors. PG - 2423-2431 LID - 10.1002/jbmr.4154 [doi] AB - A role for long non-coding RNAs (lncRNAs) in endocrine cancer pathogenesis is emerging. However, knowledge regarding their expression pattern, correlation with known genetic defects, and clinical implications in parathyroid tumors is still unclear. Here, we profiled 90 known lncRNAs in a first series of normal (PaN = 2), adenomatous (PAd = 12), and carcinomatous (PCa = 4) parathyroid glands and we confirmed deregulation of 11 lncRNAs using an independent cohort of patients (PaN = 4; PAd = 26; PCa = 9). Expression of lncRNAs was correlated with cytogenetic aberrations, status of genes multiple endocrine neoplasia 1 (MEN1) and cell division cycle 73 (CDC73), or clinical features. Globally, lncRNAs discriminate according to tissue histology. BC200 consistently identifies parathyroid cancers from adenomas and atypical adenomas. Loss-of-heterozygosity (LOH) at chromosomes 1, 11, 15, 21, and 22 significantly impacts expression of lncRNAs in PAds. Silencing of the key parathyroid gene MEN1 modulates the expression of six lncRNAs in primary PAds-derived cultures. Analogous levels of lncRNAs are measured in PAds with the mutation in the MEN1 gene compared with PAds with wild-type MEN1. Similarly, carcinomas with mutated CDC73 differ from PCas with wild-type protein in terms of expression of lncRNAs. PCas harboring CDC73 mutations overexpress BC200 compared to wild-type carcinomas. Overall, these findings shed light on deregulation of lncRNAs in human parathyroid tumors and propose that circuits between lncRNAs and the oncosuppressors MEN1 or CDC73 may have a role in parathyroid tumorigenesis as epigenetic modulators. (c) 2020 American Society for Bone and Mineral Research (ASBMR). CI - (c) 2020 American Society for Bone and Mineral Research (ASBMR). FAU - Morotti, Annamaria AU - Morotti A AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. AD - Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Forno, Irene AU - Forno I AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. AD - Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Verdelli, Chiara AU - Verdelli C AD - Laboratory of Experimental Endocrinology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, Milan, Italy. FAU - Guarnieri, Vito AU - Guarnieri V AD - Genetic Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, Foggia, Italy. FAU - Cetani, Filomena AU - Cetani F AD - Endocrine Unit, University Hospital of Pisa, Pisa, Italy. FAU - Terrasi, Andrea AU - Terrasi A AD - Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Silipigni, Rosamaria AU - Silipigni R AD - Medical Genetics Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. FAU - Guerneri, Silvana AU - Guerneri S AD - Medical Genetics Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. FAU - Andre, Valentina AU - Andre V AD - Laboratory of Experimental Endocrinology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, Milan, Italy. FAU - Scillitani, Alfredo AU - Scillitani A AD - Endocrinology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, Foggia, Italy. FAU - Vicentini, Leonardo AU - Vicentini L AD - Endocrine Surgery, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Auxologico, Milan, Italy. FAU - Ferrero, Stefano AU - Ferrero S AD - Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy. FAU - Corbetta, Sabrina AU - Corbetta S AUID- ORCID: 0000-0001-8140-3175 AD - Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy. AD - Endocrinology and Diabetology Service, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, Milan, Italy. FAU - Vaira, Valentina AU - Vaira V AD - Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200923 PL - England TA - J Bone Miner Res JT - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JID - 8610640 RN - 0 (CDC73 protein, human) RN - 0 (MEN1 protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Long Noncoding) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - *Adenoma MH - Humans MH - Loss of Heterozygosity MH - *Multiple Endocrine Neoplasia Type 1/genetics MH - *Parathyroid Neoplasms/genetics MH - Proto-Oncogene Proteins MH - *RNA, Long Noncoding/genetics MH - Tumor Suppressor Proteins/genetics OTO - NOTNLM OT - CELL DIVISION CYCLE 73 OT - EPIGENETIC OT - LONG NON-CODING RNA OT - MULTIPLE ENDOCRINE NEOPLASIA 1 OT - PARATHYROID EDAT- 2020/08/12 06:00 MHDA- 2021/07/29 06:00 CRDT- 2020/08/12 06:00 PHST- 2020/04/05 00:00 [received] PHST- 2020/07/17 00:00 [revised] PHST- 2020/08/02 00:00 [accepted] PHST- 2020/08/12 06:00 [pubmed] PHST- 2021/07/29 06:00 [medline] PHST- 2020/08/12 06:00 [entrez] AID - 10.1002/jbmr.4154 [doi] PST - ppublish SO - J Bone Miner Res. 2020 Dec;35(12):2423-2431. doi: 10.1002/jbmr.4154. Epub 2020 Sep 23.