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 journalArticle

1 Citation (Scopus)

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

Fingerprint

Apoptosis
Parathyroid Hormone
Neoplasms
MicroRNAs
Chromosomes, Human, Pair 19
Camptothecin
Parathyroid Neoplasms
Messenger RNA
Wnt Signaling Pathway
Adenoma
In Situ Hybridization
Transfection
Cell Survival
Up-Regulation
Carcinoma
Genes
Proteins

Keywords

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

ASJC Scopus subject areas

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

Cite this

The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells. / Verdelli, Chiara; Forno, Irene; Morotti, Annamaria; Creo, Pasquale; Guarnieri, Vito; Scillitani, Alfredo; Cetani, Filomena; Vicentini, Leonardo; Balza, Gianni; Beretta, Edoardo; Ferrero, Stefano; Vaira, Valentina; Corbetta, Sabrina.

In: Endocrine-Related Cancer, Vol. 25, No. 7, 01.07.2018, p. 761-771.

Research output: Contribution to journalArticle

Verdelli, Chiara ; Forno, Irene ; Morotti, Annamaria ; Creo, Pasquale ; Guarnieri, Vito ; Scillitani, Alfredo ; Cetani, Filomena ; Vicentini, Leonardo ; Balza, Gianni ; Beretta, Edoardo ; Ferrero, Stefano ; Vaira, Valentina ; Corbetta, Sabrina. / The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells. In: Endocrine-Related Cancer. 2018 ; Vol. 25, No. 7. pp. 761-771.
@article{dde9f7dca6c14e02a341452cedb44204,
title = "The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells",
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.",
keywords = "Hyperparathyroidism, LATS2, microRNA, miR-372, p21, Parathyroid tumors, Wnt/beta-catenin",
author = "Chiara Verdelli and Irene Forno and Annamaria Morotti and Pasquale Creo and Vito Guarnieri and Alfredo Scillitani and Filomena Cetani and Leonardo Vicentini and Gianni Balza and Edoardo Beretta and Stefano Ferrero and Valentina Vaira and Sabrina Corbetta",
year = "2018",
month = "7",
day = "1",
doi = "10.1530/ERC-17-0204",
language = "English",
volume = "25",
pages = "761--771",
journal = "Endocrine-Related Cancer",
issn = "1351-0088",
publisher = "BioScientifica Ltd.",
number = "7",

}

TY - JOUR

T1 - The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells

AU - Verdelli, Chiara

AU - Forno, Irene

AU - Morotti, Annamaria

AU - Creo, Pasquale

AU - Guarnieri, Vito

AU - Scillitani, Alfredo

AU - Cetani, Filomena

AU - Vicentini, Leonardo

AU - Balza, Gianni

AU - Beretta, Edoardo

AU - Ferrero, Stefano

AU - Vaira, Valentina

AU - Corbetta, Sabrina

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

KW - Hyperparathyroidism

KW - LATS2

KW - microRNA

KW - miR-372

KW - p21

KW - Parathyroid tumors

KW - Wnt/beta-catenin

UR - http://www.scopus.com/inward/record.url?scp=85049738869&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049738869&partnerID=8YFLogxK

U2 - 10.1530/ERC-17-0204

DO - 10.1530/ERC-17-0204

M3 - Article

AN - SCOPUS:85049738869

VL - 25

SP - 761

EP - 771

JO - Endocrine-Related Cancer

JF - Endocrine-Related Cancer

SN - 1351-0088

IS - 7

ER -