MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer
| dc.creator | Acón, Man Sai | |
| dc.creator | Geiß, Carsten | |
| dc.creator | Torres Calvo, Jorge | |
| dc.creator | Bravo Estupiñan, Diana | |
| dc.creator | Oviedo Blanco, Guillermo | |
| dc.creator | Arias Arias, Jorge Luis | |
| dc.creator | Rojas Matey, Luis Andres | |
| dc.creator | Báez Villalobos, Edwin | |
| dc.creator | Vásquez Vargas, Gloriana | |
| dc.creator | Oses Vargas, Yendry | |
| dc.creator | Guevara Coto, José Andrés | |
| dc.creator | Segura Castillo, Andrés | |
| dc.creator | Siles Canales, Francisco | |
| dc.creator | Quirós Barrantes, Steve | |
| dc.creator | Régnier Vigouroux, Anne | |
| dc.creator | Mendes, Pedro | |
| dc.creator | Mora Rodríguez, Rodrigo Antonio | |
| dc.date.accessioned | 2022-07-20T17:31:00Z | |
| dc.date.available | 2022-07-20T17:31:00Z | |
| dc.date.issued | 2021-12-17 | |
| dc.description.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 interac- tion network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic pa- rameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overex- press an exogenous MYC, leading to overexpression of the three microRNAs involved and downregulation of endogenous MYC. In addition, MYC overexpres- sion or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity in MYC-amplified colon cancer cells. Finally, we identified negative correlation of MYC dosage compensation with patient survival in TCGA breast cancer patients, highlighting the potential of this mechanism to prevent aneu- ploid cancer progression. | es |
| dc.description.procedence | UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET) | es |
| dc.description.procedence | UCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Salud::Maestría Académica en Bioinformática y Biología de Sistemas | es |
| dc.description.procedence | UCR::Vicerrectoría de Docencia::Ingeniería::Facultad de Ingeniería::Escuela de Ciencias de la Computación e Informática | es |
| dc.description.procedence | UCR::Vicerrectoría de Docencia::Ingeniería::Facultad de Ingeniería::Escuela de Ingeniería Eléctrica | es |
| dc.description.procedence | UCR::Vicerrectoría de Docencia | es |
| dc.identifier.citation | https://www.cell.com/iscience/home | |
| dc.identifier.doi | https://doi.org/10.1016/j.isci.2021.103407 | |
| dc.identifier.issn | 2589-0042 | |
| dc.identifier.uri | https://hdl.handle.net/10669/86990 | |
| dc.language.iso | eng | |
| dc.rights | acceso abierto | |
| dc.source | iScience, 12, 2021 | es |
| dc.subject | miRNA | es |
| dc.subject | Myc | es |
| dc.subject | Dosage compensation | es |
| dc.subject | cancer | es |
| dc.subject | Transcription factors | es |
| dc.subject | aneuploidy | es |
| dc.title | MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer | es |
| dc.type | artículo original | es |