miRNAs dictate the cell-fate decision making in cell cycle regulations
In the context of cell cycle regulation, the incoherent FFL of the Myc/E2F1/mir-17-92 network is known to control cellular proliferation and explored rigorously via theoretical and computational modeling. Here, the cluster of miRNA (mir-17-92) precisely regulates the switching to different cellular states and avoids transitions due to small perturbations79,80 in the form of growth factor present in the cellular surroundings. E2F is a group of transcription factors (E2F1, E2F2, and E2F3) that activates many genes involved in cell cycle entry and progression, and its higher expressing state commonly indicate transition from G1 to S phase. Interestingly, E2Fs are the target for miR-17-92 cluster components (Fig. 5a ). The activation of E2F1 happens in a bistable manner (Fig. 5a, right panel, orange line ), and switching from OFF to ON state happens when there is a sufficient amount of growth factor stimuli.81 In Myc/E2F1/mir-17-92 network (Fig. 5b ), Myc activates the transcription of E2F and miR-17-92, when there are a growth factor signal and miR-17-92 components, in turn, inhibit E2F1.76 E2F1 activates its transcription and also triggers Myc and miR-17-92 transcriptions. This leads to the formation of interconnected positive and negative feedback loops.76