MicroRNA inhibition fine-tunes and provides robustness to the restriction point switch of the cell cycle.
The restriction point marks a switch in G1 from growth factor-dependent to growth factor-independent progression of the cell cycle. The proper regulation of this switch is important for normal cell processes; aberrations could result in a number of diseases such as cancer, neurodegenerative disorders, stroke and myocardial infarction. To further understand the regulation of the restriction point, we extended a mathematical model of the Rb-E2F pathway to include members of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs play an essential role in fine-tuning and providing robustness to the switch. We also demonstrate how microRNA regulation can steer cells in or out of cancer states.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA 02142, USA.
Ricardo C H
RC
Del Rosario
Institute of Mathematics, University of the Philippines, Diliman, Quezon City 1101 Philippines.
Joseph Ray Clarence G
JR
Damasco
Philippine Genome Center, University of the Philippines, Diliman, Quezon City 1101 Philippines.
Baltazar D
BD
Aguda
D002453:Cell Cycle; D050684:E2F Transcription Factors / Q000235:genetics*; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008962:Models, Theoretical; D009369:Neoplasms / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D015398:Signal Transduction
D050684:E2F Transcription Factors; D035683:MicroRNAs; D016160:Retinoblastoma Protein