0000000000315924
AUTHOR
Gloriana Vásquez-vargas
MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer
SummaryWe 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 multi-omics data and developed a biocomputational platform to construct a mathematical model of their interaction network with miRNAs 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 with a novel genetic tug-of-war technique by overexpressing an exogenous MYC leading to over-expression of the three microR…
MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer
Summary 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 …
<i>MYC</i> Dosage Compensation is Mediated by miRNA-Transcription Factor Interactions in Aneuploid Cancer
Cancer complexity is consequence of genomic instability leading to aneuploidy. We hypothesize that dosage compensation of critical genes arise from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We developed a computational platform to identify a network of miRNAs and transcription factors interacting with candidate dosage-compensated genes using NCI-60 multi-omic data. We next constructed a mathematical model where the property of dosage compensation emerged for MYC and STAT3 and was dependent on the kinetic parameters of their feedback and feed-forward interactions with four miRNAs. We developed a genetic tug-of-war approach by overexpressing an…