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