Figure 3.

MiRNAs regulates autophagy by targeting E3 ubiquitin ligases or DUBs. Once receiving autophagy induction signals, ULK1 complex mediates the initiation of autophagy, and PI3KC3 complex participates in the nucleation of phagophore. Under the action of two ubiquitin-like systems, phagophore is continuously extended to form autophagosome, which eventually fused with lysosome to form autolysosome and the contents of the autolysosome are then degraded and exported back into the cytoplasm for reuse by the cell. (a) Mir-30a targets both MARCH5 and ATG5, MARCH5 RNA serves as a competing endogenous RNA (ceRNA) to regulate the expression of ATG5 by competing with ATG5 for mir-30a. (b) ATG7 and MARCH7 mRNA, as ceRNAs, regulate each other by competing for mir-200a. (c) Mir-233 increases autophagy by negatively targeting TRIM37, which promotes the mTORC1 pathway. (d) As a ubiquitin ligase of TNRC6, a component of miRISC, TRIM65 blocks the function of miRISC to achieve the effect of inhibiting mir-138-5p. However, ATG7 was upregulated by TRIM65 as a target of mir-138-5p. (e) Mir-34a-5p promotes autophagy by directly targeting SYVN1. (f) Mir-146a inhibits E3 ubiquitin ligase TRAF6, which has a positive regulatory effect on ULK1 protein through K63-linked ubiquitination. (g) Mir-27 targets NEDD4, the E3 ubiquitin ligase of Notch1, increasing Notch1 protein expression and decreasing autophagy. (h) Mir-6825-5p, mir-6845-5p, mir-6886-3p and mir-29c can directly target USP22, the DUB of Sirt1, and ultimately suppress Sirt1-mediated autophagy. (i) Mir-26b negatively targets USP9X, a DUB of p53, and affects autophagy by inducing p53 degradation. (j) Mir-26a negatively targets USP15, which inhibits autophagy.