MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer.

ABSTRACT: We hypothesize that dosage compensation of critical genes arises from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multiomics data and developed a biocomputational platform to construct a mathematical model of their interaction network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic parameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overexpress an exogenous MYC, leading to overexpression of the three microRNAs involved and downregulation of endogenous MYC. In addition, MYC overexpression or

SUBMITTER: Acon M 

PROVIDER: S-EPMC8627999 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature