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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Molecular Cancer 1/2018

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

Zeitschrift:
Molecular Cancer > Ausgabe 1/2018
Autoren:
Joëlle El Hajj, Eric Nguyen, Qingyuan Liu, Claire Bouyer, Eric Adriaenssens, George Hilal, Evelyne Ségal-Bendirdjian
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12943-018-0835-8) contains supplementary material, which is available to authorized users.

Abstract

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.
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