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  • The Oncosuppressors MEN1 and CDC73 Are Involved in lncRNA Deregulation in Human Parathyroid Tumors.

The Oncosuppressors MEN1 and CDC73 Are Involved in lncRNA Deregulation in Human Parathyroid Tumors.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2020-08-12)
Annamaria Morotti, Irene Forno, Chiara Verdelli, Vito Guarnieri, Filomena Cetani, Andrea Terrasi, Rosamaria Silipigni, Silvana Guerneri, Valentina Andrè, Alfredo Scillitani, Leonardo Vicentini, Stefano Ferrero, Sabrina Corbetta, Valentina Vaira
ABSTRACT

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).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Vinculin antibody produced in mouse, clone VIN-11-5, ascites fluid
Sigma-Aldrich
MISSION® esiRNA, targeting human MEN1
Sigma-Aldrich
MISSION® esiRNA, targeting FLUC
Sigma-Aldrich
Anti-β-Tubulin antibody, Mouse monoclonal, ~2.0 mg/mL, clone AA2, purified from hybridoma cell culture