Abstract
Original language | English |
---|---|
Pages (from-to) | 2423-2431 |
Number of pages | 9 |
Journal | J. Bone Miner. Res. |
Volume | 35 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- CELL DIVISION CYCLE 73
- EPIGENETIC
- LONG NON-CODING RNA
- MULTIPLE ENDOCRINE NEOPLASIA 1
- PARATHYROID
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The Oncosuppressors MEN1 and CDC73 Are Involved in lncRNA Deregulation in Human Parathyroid Tumors : Journal of Bone and Mineral Research. / Morotti, A.; Forno, I.; Verdelli, C.; Guarnieri, V.; Cetani, F.; Terrasi, A.; Silipigni, R.; Guerneri, S.; Andrè, V.; Scillitani, A.; Vicentini, L.; Ferrero, S.; Corbetta, S.; Vaira, V.
In: J. Bone Miner. Res., Vol. 35, No. 12, 2020, p. 2423-2431.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The Oncosuppressors MEN1 and CDC73 Are Involved in lncRNA Deregulation in Human Parathyroid Tumors
T2 - Journal of Bone and Mineral Research
AU - Morotti, A.
AU - Forno, I.
AU - Verdelli, C.
AU - Guarnieri, V.
AU - Cetani, F.
AU - Terrasi, A.
AU - Silipigni, R.
AU - Guerneri, S.
AU - Andrè, V.
AU - Scillitani, A.
AU - Vicentini, L.
AU - Ferrero, S.
AU - Corbetta, S.
AU - Vaira, V.
N1 - Export Date: 24 February 2021 CODEN: JBMRE Correspondence Address: Vaira, V.; Division of Pathology, Italy; email: valentina.vaira@unimi.it Correspondence Address: Corbetta, S.; Department of Biomedical, Italy; email: sabrina.corbetta@unimi.it Correspondence Address: Corbetta, S.; Endocrinology and Diabetology Service, Italy; email: sabrina.corbetta@unimi.it Funding details: GR2011-02351626 Funding details: Università degli Studi di Milano, UniMi Funding text 1: This research was supported by the Italian Ministry of Health GR2011-02351626 (to VV), Italian Ministry of Health Ricerca Corrente program (to SF, SC, and CV), and by Linea 2 research fund of University of Milan (to SC). AM was supported by a fellowship from the Doctorate School of Molecular and Translational Medicine at the University of Milan. All data generated or analyzed during this study are included in this article and its additional information files. Author contributions: AM: Data curation; formal analysis; investigation; methodology; writing-original draft. IF: Data curation; investigation. CV: Data curation; formal analysis; investigation; methodology. VG: Data curation; investigation; methodology; resources. FC: Data curation; resources; writing-review and editing. AT: Formal analysis; software; validation. RS: Formal analysis; investigation; methodology; validation. VA: Data curation; formal analysis; investigation; methodology. AS: Data curation; investigation; resources; writing-review and editing. LV: Investigation; resources. SF: Data curation; methodology; validation. SC: Conceptualization; funding acquisition; project administration; resources; supervision; validation; visualization; writing-review and editing. VV: Conceptualization; formal analysis; methodology; project administration; visualization; supervision; writing-review and editing; funding acquisition. Funding text 2: This research was supported by the Italian Ministry of Health GR2011‐02351626 (to VV), Italian Ministry of Health Ricerca Corrente program (to SF, SC, and CV), and by Linea 2 research fund of University of Milan (to SC). AM was supported by a fellowship from the Doctorate School of Molecular and Translational Medicine at the University of Milan. All data generated or analyzed during this study are included in this article and its additional information files. 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(2007) Eur J Endocrinol, 156 (5), pp. 547-554; Bollerslev, J., Schalin-Jäntti, C., Rejnmark, L., Unmet therapeutic, educational and scientific needs in parathyroid disorders: Consensus Statement from the first European Society of Endocrinology Workshop (PARAT) (2019) Eur J Endocrinol, 181 (3), pp. P1-19; Sharretts, J.M., Kebebew, E., (2010) Parathyroid Cancer. 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PY - 2020
Y1 - 2020
N2 - 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. © 2020 American Society for Bone and Mineral Research (ASBMR). © 2020 American Society for Bone and Mineral Research (ASBMR)
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. © 2020 American Society for Bone and Mineral Research (ASBMR). © 2020 American Society for Bone and Mineral Research (ASBMR)
KW - CELL DIVISION CYCLE 73
KW - EPIGENETIC
KW - LONG NON-CODING RNA
KW - MULTIPLE ENDOCRINE NEOPLASIA 1
KW - PARATHYROID
U2 - 10.1002/jbmr.4154
DO - 10.1002/jbmr.4154
M3 - Article
VL - 35
SP - 2423
EP - 2431
JO - J. Bone Miner. Res.
JF - J. Bone Miner. Res.
SN - 0884-0431
IS - 12
ER -