Table 1.
CircRNAs are involved in regulating liver fibrosis.
| CircRNAs | Targets | Biological Function | Expression Pattern | Ref. |
|---|---|---|---|---|
| Inhibition of liver fibrosis | ||||
| CircRNA SCAR | ATP5B | CircRNA SCAR overexpression clearly inhibit the contractility, collagen and α-SMA expression in NASH fibroblasts, thereby alleviating the fibrotic phenotype. | decrease | [46] |
| CircCREBBP | hsa-miR-1291 | CircCREBBP, as a sponge for hsa-miR-1291, promotes the expression of LEFTY2 and inhibits the activation of hepatic stellate cells. | decrease | [54] |
| CircFBXW4 | miR-18b-3p | CircFBXW4, as a miRNA sponge for miR-18b-3p, to regulate the expression of FBXW7, inhibiting the activation of hepatic stellate cells. | decrease | [21] |
| CircPSD3 | miR-92b-3p | CircPSD3 can inhibit HSC activation and proliferation by targeting the miR-92b-3p/Smad7 axis to alleviate the formation of liver fibrosis. | decrease | [12] |
| Hsa_circ_0070963 | miR-223-3p | Hsa_circ_0070963, as a miR-223-3p sponge, inhibites HSC activation via regulation of miR-223-3p and LEMD3 in liver fibrosis. | decrease | [58] |
| Hsa_circ_0004018 | hsa-miR-660-3p | Hsa_circ_0004018 acts as a sponge of hsa-miR-660-3p, and then targetedly suppress the expression of TEP1 to inhibit the activation of HSCs. | decrease | [22] |
| Mmu_circ_34116 | miR-22 | Mmu_circ_34116 inhibits the activation of HSCs and fibrosis by mmu_circ_34116/miR-22/BMP7 signal axis. | decrease | [59] |
| CircDIDO1 | miR-141-3p | Extracellular circDIDO1 restraines HSC activation by miR-141-3p/PTEN/AKT pathway in liver fibrosis. | decrease | [60] |
| CircMTO1(Hsa_circ_0007874) | miR-17-5p, miR-181b-5p | CircMTO1 can inhibit TGF-β1-induced HSC activation by targeting miR-17-5p and Smad7 or miR-181b-5p/PTEN/AKT cascade. | decrease | [6,61] |
| CircRNA-0046367 | miR-34a | CircRNA-0046367 promotes the expression of CPT2 and ACBD3 by promoting PPARα through CircRNA-0046367/miR-34a/PPARα axis, and reduces steatosis of hepatocytes. | decrease | [63] |
| Mmu_circ_0000623 | miR-125 | Mmu_circ_0000623-modified ADSCs, significantly suppressed CCl4-induced liver fibrosis by promoting autophagy activation through interacting with the miR-125/ATG4D. | decrease | [62] |
| CircRNA-608 | miR-222 | CircRNA-608 might promote PINK1-mediated mitophagy to slow down NASH-related liver fibrosis though inhibiting miR-222 in lipotoxic HSCs. | decrease | [64] |
| LNCPINT-derived CircRNAs (Circ_0001452, Circ_0001453, and Circ_0001454) | miR-466i-3p, miR-669c-3p | Loss of LNCPINT-derived CircRNAs may underlie NAFLD via miR-466i-3p and miR-669c-3p-dependent inactivation of the AMPK signaling pathway. | decrease | [65] |
| MecciRNAs (Hsa_circ_0089761 and Hsa_circ_0089763) | miR-642a-5p, miR-1248, miR-670-3p and miR-1224-3p | Hsa_ circ_0089761 and hsa_circ_0089763 could function as competing for endogenous RNAs (ceRNAs) to regulate fibrosis-related signals. | decrease | [66] |
| MecciRNAs (Hsa_circ_0089762 and Hsa_circ_0008882_ | Hsa_circ_0089762 and hsa_circ_0008882 might act as molecular scaffolds to regulate specific complex functions or serve as molecular chaperones in the folding of mitochondria-imported proteins. | decrease | [67,68] | |
| Promotion of liver fibrosis | ||||
| CircUbe2k(Mmu_circ_0001350) | miR-149-5p | CircUbe2k could promote the activation of HSCs and the progress of HF through the CircUbe2k/miR-149-5p/TGF-β2 axis. | increase | [55] |
| CircPWWP2A | miR-203, miR-223 | CircPWWP2A promoted the activation and proliferation of HSCs via sponging miR-203 and miR-223, subsequently enhanced the expression of Fstl1 and Tlr4, respectively, and eventually promoted hepatic fibrosis. | increase | [4] |
| CircRNA-4099 | miR-706 | CircRNA-4099 aggravated H2O2-induced damage and fibrosis by inhibiting miR-706 through triggering keap1/Nrf2 and p38MAPK in L02 cell lines. | increase | [69] |
| CircRNA-0067835 | miR-155 | CircRNA-0067835 can promote liver fibrosis progression by acting asa sponge of miR-155 to promote FOXO3a and AKT expression in LX-2 cells. | increase | [70] |
| CircRSF1 | miR-146a-5p | CircRSF1 can promote the activation of HSC cells by the CircRSF1/miR-146a-5p/RAC1 axis in irradiated LX-2 cells. | increase | [71] |
| Hsa_circ_0071410 | miR-9-5p | Hsa_circ_0071410 inhibits the proliferation of LX-2 by Hsa_circ_0071410/miR-9-5p in irradiated LX-2cells. | increase | [57] |
| CircTUBD1(Hsa_circ_0044897) | miR-203a-3p | CircTUBD1 regulated the activation and fibrosis response of LX-2 cells induced by irradiation via circTUBD1/miR-203a-3p/Smad3 axis. | increase | [72] |
| Hsa_circ_0072765 | miR-197-3p | Hsa_circ_0072765 promotes the progression of HSCs and liver fibrosis induced by TGF-β through decreasing the expression of miR-197-3p and inducing the expression of TRPV3. | increase | [73] |
| CircMcph1 | miR-370-3p | CircMcph1 could regulate the expression of Irak2 by sponging miR-370-3p. | increase | [74] |
| CircRNA-0008494 | miR-185-3p | CircRNA-0008494 can regulate activation, proliferation, migration and apoptosis of HSCs by CircRNA-0008494/miR-185-3p/Col1a1 axis. | increase | [75] |
Several CircRNAs (e.g., CircCREBBP, CircFBXW4, CircPSD3, hsa_circ_0070963, hsa_circ_0004018, mmu_circ_34116, CircDIDO1, CircMTO1 and mmu_circ_0000623 et al.) have been demonstrated to inhibit liver fibrosis. Some CircRNAs are upregulated in liver fibrotic.tissues and HSCs, which promote the progression of liver fibrosis through multiple mechanisms (e.g., acting as miRNA sponges, binding to functional miRNAs, and regulating gene expression at the transcriptionalor post-transcriptional level).