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MYC is downregulated by a mitochondrial checkpoint mechanism.

ABSTRACT: The MYC proto-oncogene serves as a rheostat coupling mitogenic signaling with the activation of genes regulating growth, metabolism and mitochondrial biogenesis. Here we describe a novel link between mitochondria and MYC levels. Perturbation of mitochondrial function using a number of conventional and novel inhibitors resulted in the decreased expression of MYC mRNA. This decrease in MYC mRNA occurred concomitantly with an increase in the levels of tumor-suppressive miRNAs such as members of the let-7 family and miR-34a-5p. Knockdown of let-7 family or miR-34a-5p could partially restore MYC levels following mitochondria damage. We also identified let-7-dependent downregulation of the MYC mRNA chaperone, CRD-BP (coding region determinant-binding protein) as an additional control following mitochondria damage. Our data demonstrates the existence of a homeostasis mechanism whereby mitochondrial function controls MYC expression.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5685744 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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MYC is downregulated by a mitochondrial checkpoint mechanism.

Zhang Xiaonan X Mofers Arjan A Hydbring Per P Olofsson Maria Hägg MH Guo Jing J Linder Stig S D'Arcy Padraig P

Oncotarget 20171006 52

The MYC proto-oncogene serves as a rheostat coupling mitogenic signaling with the activation of genes regulating growth, metabolism and mitochondrial biogenesis. Here we describe a novel link between mitochondria and MYC levels. Perturbation of mitochondrial function using a number of conventional and novel inhibitors resulted in the decreased expression of MYC mRNA. This decrease in MYC mRNA occurred concomitantly with an increase in the levels of tumor-suppressive miRNAs such as members of the ...[more]

PMID: 29163823

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