Title :

Telomerase regulation by the long non-coding RNA H19 in human acute promyelocytic leukemia cells

Author(s) :

El Hajj, Joëlle [Auteur]
Nguyen, Eric [Auteur]
Liu, Qingyuan [Auteur]
Bouyer, Claire [Auteur]
Adriaenssens, Eric [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Hilal, George [Auteur]
Ségal-Bendirdjian, Evelyne [Auteur]

Journal title :

Molecular Cancer

Pages :

85

Publisher :

BioMed Central

Publication date :

2018-04-27

ISSN :

1476-4598

English keyword(s) :

Telomerase hTERT hTR H19 long non-coding RNA Retinoids Acute promyelocytic leukemia
Telomerase
hTERT
hTR
H19 long non-coding RNA
Retinoids
Acute promyelocytic leukemia

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background: Since tumor growth requires reactivation of telomerase (hTERT), this enzyme is a challenging target for drug development. Therefore, it is of great interest to identify telomerase expression and activity ...
Show more >Background: Since tumor growth requires reactivation of telomerase (hTERT), this enzyme is a challenging target for drug development. Therefore, it is of great interest to identify telomerase expression and activity regulators. Retinoids are well-known inducers of granulocytic maturation associated with hTERT repression in acute promyelocytic leukemia (APL) blasts. In a maturation-resistant APL cell line, we have previously identified a new pathway of retinoid-induced hTERT transcriptional repression independent of differentiation. Furthermore, we reported the isolation of a cell variant resistant to this repression. Those cell lines could serve as unique tools to identify new telomerase regulators. Methods: Using a microarray approach we identified the long non-coding RNA, H19 as a potential candidate playing a role in telomerase regulation. Expression of H19, hTERT, and hTR were examined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Telomerase activity was quantified by quantitative telomeric repeats amplification protocol (qTRAP). In vitro and in vivo assays were performed to investigate H19 function on telomerase expression and activity. Results: We showed both in retinoid-treated cell lines and in APL patient cells an inverse relationship between the expression of H19 and the expression and activity of hTERT. Exploring the mechanistic link between H19 and hTERT regulation, we showed that H19 is able to impede telomerase function by disruption of the hTERT-hTR interaction. Conclusions: This study identifies a new way of telomerase regulation through H19's involvement and thereby reveals a new function for this long non-coding RNA that can be targeted for therapeutic purpose.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL