Human telomerase reverse transcriptase in papillary thyroid cancer: gene expression, effects of silencing and regulation by BET inhibitors in thyroid cancer cells.
BET inhibitors
Papillary thyroid cancer
phospho-AKT
siRNA anti-hTERT
Journal
Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
14
11
2018
accepted:
29
12
2018
pubmed:
21
1
2019
medline:
28
4
2020
entrez:
21
1
2019
Statut:
ppublish
Résumé
Mutations in TERT promoter have been detected in the more aggressive papillary thyroid cancers (PTCs). To elucidate the role of TERT as an eligible molecular target in these tumors, the expression of hTERT was analyzed in a series of PTCs and the effects of both pharmacological and RNA-interference-induced hTERT silencing were investigated in two human PTC cell lines (K1 and BCPAP). The expression levels of hTERT mRNA and protein were evaluated by real-time PCR and western blot assays, respectively. Effects of hTERT silencing on PTC cell lines were analyzed by MTT, migration and western blot assays. Pharmacological inhibition of hTERT was performed using two bromodomain and extra-terminal (BET) inhibitors, JQ1 and I-BET762. hTERT expression results increased in 20 out of 48 PTCs, including tumors either positive or negative for the presence of hTERT promoter and/or BRAF mutations. In K1 and BCPAP cells, hTERT silencing determined a reduction in cell viability (~50% for K1 and ~70%, for BCPAP, vs control) and migration properties that were associated with a decrease of AKT phosphorylation and β-Catenin expression. Moreover, hTERT mRNA levels were down-regulated by two BET inhibitors, JQ1 and I-BET762, which at the same dosage (0.5 and 5 µM) reduced the growth of these thyroid cancer cells. These findings demonstrate that hTERT may represent an excellent therapeutic target in subgroups of aggressive PTCs.
Identifiants
pubmed: 30661164
doi: 10.1007/s12020-018-01836-2
pii: 10.1007/s12020-018-01836-2
doi:
Substances chimiques
(+)-JQ1 compound
0
Azepines
0
Proteins
0
Triazoles
0
bromodomain and extra-terminal domain protein, human
0
Benzodiazepines
12794-10-4
molibresib
5QIO6SRZ2R
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
545-553Références
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