The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells

Chiara Verdelli, Irene Forno, Annamaria Morotti, Pasquale Creo, Vito Guarnieri, Alfredo Scillitani, Filomena Cetani, Leonardo Vicentini, Gianni Balza, Edoardo Beretta, Stefano Ferrero, Valentina Vaira, Sabrina Corbetta

Research output: Contribution to journalArticlepeer-review

Abstract

Parathyroid tumors deregulate microRNAs belonging to the two clusters on the chromosome 19, the C19MC and miR-371-373 clusters. Here, we report that the embryonic miR-372 is aberrantly expressed in half of parathyroid adenomas (PAds) in most of atypical adenomas and carcinomas (n = 15). Through in situ hybridization, we identified that miR-372-positive parathyroid tumor cells were scattered throughout the tumor parenchyma. In PAd-derived cells, ectopic miR-372 inhibited the expression of its targets CDKN1A/p21 and LATS2 at both mRNA and protein levels. Although the viability of parathyroid cells was not affected by miR-372 overexpression, the miRNA blunted camptothecin-induced apoptosis in primary PAd-derived cultures. miR-372 overexpression in parathyroid tumor cells increased parathormone (PTH) mRNA levels, and it positively correlated in vivo with circulating PTH levels. Conversely, the parathyroid-specific genes TBX1 and GCM2 were not affected by miR-372 mimic transfection. Finally, miR-372 dampened the Wnt pathway in parathyroid tumor cells through DKK1 upregulation. In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling.

Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalEndocrine-Related Cancer
Volume25
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

Keywords

  • Hyperparathyroidism
  • LATS2
  • microRNA
  • miR-372
  • p21
  • Parathyroid tumors
  • Wnt/beta-catenin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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