Figure 2.

Examples of microRNAs and transcription factors forming a dynamic control circuit for switching between transcriptional states. a, ZEB1 activates and suppresses the expression of mesenchymal and epithelial marker genes, respectively. It and miR-200 family reciprocally inhibit each other, constituting a negative feedback loop (upper panel). When the input signal (TGF-β) reaches over a threshold level, the system will switch from epithelial-high to mesenchymal-high state (lower panel; adopted from Stallaert et al (Stallaert et al., 2019)). Solid and dashed curve, stable and unstable state, respectively. This figure is adopted from b, Incorporation of another negative feedback loop (SNAIL1 and miR-34) to ZEB1/miR-200 family circuit (upper panel) results in an additional state (EMT, lower panel; adopted from Zhang et al (Zhang et al., 2014)). As the input signal (TGF-β) keeps increasing, the system will switch from epithelial-high to EMT, and then to mesenchymal-high state (lower panel). c, An example of the collaborative behavior of miRNA. A gene can be targeted by multiple miRNA (e.g. VIM1, MAF, and CXCL12 are targeted by both miR-200c-3p and miR-141–3p), but each miRNA can target multiple genes in which some of them might not be shared with other miRNAs (e.g. miR-200–3p targeting VIM1 and FSTL1) (Guo et al., 2014). Part of the figure is generated using birender.com (2022).