The OncosuppressorsMEN1andCDC73Are Involved inlncRNADeregulation in Human Parathyroid Tumors

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 genesmultiple endocrine neoplasia 1(MEN1) andcell division cycle 73(CDC73), or clinical features. Globally, lncRNAs discriminate according to tissue histology.BC200consistently 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 geneMEN1modulates 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 mutatedCDC73differ from PCas with wild-type protein in terms of expression of lncRNAs. PCas harboringCDC73mutations overexpressBC200compared 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 oncosuppressorsMEN1orCDC73may have a role in parathyroid tumorigenesis as epigenetic modulators. (c) 2020 American Society for Bone and Mineral Research (ASBMR).