Abstract: To evaluate the effect of long noncoding RNA (lncRNA) lnc-ISG20 on transforming growth factor β1(TGF-β1)-induced hepatic stellate cell activation and explore the mechanism of silencing lnc-ISG20 in anti-liver fibrosis. The GEO database was used to analyze the differential expression of lnc-ISG20 in liver fibrosis tissue and normal liver tissue. The liver fibrosis cell model was established by treating human hepatic stellate cells LX-2 with 10 ng/mL TGF-β1 and then divided into sh-NC group and sh-lnc-ISG20 group, which were transfected with sh-NC plasmid and sh-lnc-ISG20 plasmid, respectively. CCK-8 assay was used to detect the growth curve of LX-2 cells in each group. Flow cytometry was used to detect the cell cycle distribution and apoptosis rate of LX-2 cells in each group. Dual luciferase reporter assay was used to verify the targeting relationship between lnc-ISG20 and miR-20a-5p. The GEO database was used to analyze the correlation between the expression of lnc-ISG20 and miR-20a-5p in liver fibrosis tissues. qRT-PCR was used to detect the expression level of miR-20a-5p in each group of cells. Western blotting was used to detect the expression levels of p-P38, p-IκB, p-P65 and p-ASK1 proteins in the MAPK/NF-κB signaling pathway. Compared with normal liver tissue, the expression of lnc-ISG20 in liver fibrosis tissue increased (P<0.01). Compared with the sh-NC group, the proliferation activity of LX-2 cells in the sh-lnc-ISG20 group decreased (P<0.05), the cell cycle was blocked (P<0.01), and the apoptosis rate increased (P<0.01). miR-20a-5p was a target gene of lnc-ISG20 (P<0.01). The expression of lnc-ISG20 is negatively correlated with miR-20a-5p in liver fibrosis tissue (P<0.01). Compared with the sh-NC group, the expression of miR-20a-5p in LX-2 cells in the sh-lnc-ISG20 group increased (P<0.01), and the expressions of p-P38, p-IκB, p-P65 and p-ASK1 proteins of the MAPK/NF-κB signaling pathway all decreased (all P<0.01). Silencing lnc-ISG20 inhibits TGF-β1-induced proliferation of LX-2 cells and promotes apoptosis by increasing miR-20a-5p expression. lnc-ISG20 is expected to become a molecular target for the treatment of liver fibrosis.
Key words: liver fibrosis; lnc-ISG20; miR-20a-5p; hepatic stellate cells; cell apoptosis
（Acta Laser Biology Sinica, 2025, 34(5): 451-458）