PT - JOURNAL ARTICLE AU - Sengupta, Dola AU - Govindaraj, Vinodhini AU - Kar, Sandip TI - Subtle alteration in microRNA dynamics accounts for differential nature of cellular proliferation AID - 10.1101/214429 DP - 2017 Jan 01 TA - bioRxiv PG - 214429 4099 - http://biorxiv.org/content/early/2017/11/05/214429.short 4100 - http://biorxiv.org/content/early/2017/11/05/214429.full AB - In the G1 phase of the mammalian cell cycle, a bi-stable steady state dynamics of the transcription factor E2F ensures that only a certain threshold level of the growth factor can induce a high expression level (on state) of E2F to initiate either normal or abnormal cellular proliferation or even apoptosis. A group of microRNA’s known as the mir-17-92 cluster, which specifically inhibits E2F, can simultaneously influence the threshold level of growth factor required for E2F activation, and the corresponding expression level of E2F in the on state. However, mir-17-92 cluster can function as either oncogene or tumor suppressor in a cell-type specific manner for reasons that still remain illusive. Here we put forward a deterministic mathematical model for Myc/E2F/mir-17-92 network that demonstrates how the experimentally observed mir-17-92 mediated differential nature of the cellular proliferation can be reconciled by having conflicting steady state dynamics of E2F for different cell types. While a 2-D bifurcation study of the model rationalizes the reason behind the contrasting E2F dynamics, an intuitive sensitivity analysis of the model parameters predicts that by exclusively altering the mir-17-92 related part of the network, it is possible to experimentally manipulate the cellular proliferation in a cell-type specific fashion for therapeutic intervention.