期刊
ONCOTARGET
卷 9, 期 4, 页码 5016-5031出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.23579
关键词
Pol I-nucleolar rRNA transcription; POLRMT-mitochondrial rRNA transcription; MYC-driven proliferation; Pol I and POLRMT inhibitors
资金
- NCI [R01 CA127614, P30 CA016056]
- RPCI-UPCI Ovarian Cancer Spore DRP award
The MYC transcription factor coordinates, via different RNA polymerases, the transcription of both ribosomal RNA (rRNA) and protein genes necessary for nucleolar as well as mitochondrial ribogenesis. In this study we tested if MYC-coordination of rRNA transcription in the nucleolus and in the mitochondrion drives (cancer) cell proliferation. Here we show that the anti-proliferative effect of CX-5461, a Pol I inhibitor of rRNA transcription, in ovarian (cancer) cell contexts characterized by MYC overexpression is enhanced either by 2'-C-Methyl Adenosine (2'-C-MeA), a ribonucleoside that inhibits POLRMT mitochondrial rRNA (mt-rRNA) transcription and doxycycline, a tetracycline known to affect mitochondrial translation. Thus, hindering not only mt-rRNA transcription, but also mitoribosome function in MYC-overexpressing ovarian (cancer) cells, potentiates the antiproliferative effect of CX-5461. Targeting MYC-regulated rRNA transcription and ribogenesis in both the nucleolus and mitochondrion seems to be a novel approach worth of consideration for treating MYC-driven cancer.
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