Genomics

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MST-312: a telomerase inhibitor effectively blocking MYC oncogenic functions [array]


ABSTRACT: Reactivation of the telomerase reverse transcriptase subunit, TERT, is linked to tumourigenesis due to well-documented telomere-dependent and independent functions. The aim of this study was to investigate the effect of the telomerase inhibitor, MST-312, on TERT functions, focusing in particular, on its effects on MYC stabilty and MYC-regulated pathways, in order to assess its potential as a therapeutic agent. We demonstrate that MST-312 reduces MYC levels in cancer cells, leading to reduced MYC levels on chromatin, and subsequently affecting the MYC-regulated transcriptional program. As a result, MST-312 treatment increases the survival of lymphoma-bearing mice. Mechanistically, MST-312 affects the conformation of TERT, leading to TERT/Terc dissociation, and the subsequent loss of both its telomere-dependent and independent functions. Based on the presented data, we conclude that MST-312 treatment is a promising therapeutic strategy, in particular, in MYC-driven tumorus. Overall design: Total RNA was extracted from P493 cells treated with MST-312 and TET for 48 h, then released into fresh TET-free media with MST-312 for 0, 4, 8 and 24 hours.

INSTRUMENT(S): Illumina HumanHT-12 V4.0 expression beadchip

ORGANISM(S): Homo sapiens  

SUBMITTER: Julius Müller 

PROVIDER: GSE77014 | GEO | 2020-01-01

REPOSITORIES: GEO

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