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. 2023 Jan 23;24(3):2233. doi: 10.3390/ijms24032233

Figure 2.

Figure 2

Multiple miRNA-mediated circuits. A common miRNA-mediated feed-forward loop (FFL) includes a master transcription factor (TF) regulating a miRNA and an mRNA target gene. miRNA-mediated FFLs are divided into type I (incoherent) or type II (coherent) FFLs, which are determined by the association of the miRNA transcription and the target gene (co-regulation or opposing regulation by the same TF). (A) In Type I circuits (incoherent action), TFs positively regulate miRNA and their target mRNAs and aim to define and maintain protein homeostasis, especially in cell populations that have high sensitivity to the target mRNA. (B) In Type II circuits (coherent action), transcriptional activation or repression (positive or negative FFL) of a target mRNA by a TF is allowed, resulting in synergistic miRNA expression. In the case of mRNA repression, the TF downregulates the target mRNA and upregulates the miRNA. In the case of mRNA upregulation, the TF upregulates the mRNA, resulting in synergistic miRNA suppression. (C) Intronic miRNA-mediated self-loop (iMSL) consists of a TF that regulates both the miRNA and a host mRNA gene encoded by a single genomic site. In this loop, the miRNA is usually placed in an intron of the host gene, and transcription occurs at the same time; thus, the TF regulates the miRNA and the host gene in the same way. (D) In miRNA-modulated FFL, the miRNA acts as a master regulator and controls a TF. In this circuit, the interaction between the TF and the target can be both activating and repressive. (E) In the double negative feedback loop in the presence of an epigenetic regulator, the miRNA targets the epigenetic regulator, while the expression of the same miRNA is controlled by the epigenetic regulator. In this circuit, both the miRNA regulation of a target gene and the regulation of an epigenetic regulator of the miRNA are negative. (F) In the sponge circuit, the long non-coding RNAs (lncRNAs) control target genes through a miRNA-dependent mechanism. The miRNA controls both the target mRNA and the lncRNAs through the miRNA recognition elements (MREs).