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

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 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 , leading to overexpression of the three microRNAs involved and downregulation of endogenous In addition, overexpression or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity in -amplified colon cancer cells.