Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR‐146a‐5p

Abstract

The role of circular RNA (circRNA) in radiation‐induced liver disease (RILD) remains largely unknown. In this study, Ras‐related C3 botulinum toxin substrate 1 (RAC1) was elevated in irradiated human hepatic stellate cell (HSC) line LX2, the important effector cell mediating RILD. Overexpression of RAC1 promotes cell proliferation, proinflammatory cytokines production, and α‐smooth muscle actin expression, which were blocked by microRNA (miR)‐146a‐5p mimics. CircRNA RSF1 (circRSF1) was upregulated in irradiated LX2 cells and predicted to harbor binding site for miR‐146a‐5p. Biotinylated‐RNA pull down and dual‐luciferase reporter detection confirmed the direct interaction of circRSF1 and miR‐146a‐5p. Enforced expression of circRSF1 increased RAC1 expression by acting as miR‐146a‐5p sponge to inhibit miR‐146a‐5p activity, and thus enhanced the cell viability, and promoted inflammatory and fibrotic phenotype of irradiated LX2 cells. These findings indicate a functional regulatory axis composing of circRSF1, miR‐146a‐5p, and RAC1 in irradiated HSC, which may provide attractive therapeutic targets for RILD.

Analysis and Validation of circRNA-miRNA Network in Regulating m6A RNA Methylation Modulators Reveals CircMAP2K4/miR-139-5p/YTHDF1 Axis Involving the Proliferation of Hepatocellular Carcinoma

“…As the sponge of miRNA, the expression level of circRNA usually does not influence the expression of miRNA. In addition, some miRNAs may inhibit highly expressed mRNA in a compensatory elevated expression manner ( 18 ). Therefore, the selection of circRNA-miRNA or miRNA-mRNA pairs was not limited by their expression patterns that must be reversed.…”

Construction of a circRNA-miRNA-mRNA Network Related to Macrophage Infiltration in Hepatocellular Carcinoma

“…As the sponge of miRNAs, the expression level of circRNAs usually does not affect the expression of miRNAs. In addition, some miRNAs may suppress highly expressed mRNAs in a compensatory elevated expression manner ( Chen et al, 2020 ). Thus, circRNA-miRNA and miRNA-mRNA pairs were selected without the constraint that their expression patterns must be different.…”

Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma

“…Generally, circRNAs do not affect the expression of miRNAs after adsorbing miRNAs. In addition, some miRNAs can inhibit highly expressed mRNAs in an antagonistic up-regulated manner ( Chen et al, 2020 ). Therefore, the choice of circRNA-miRNA or miRNA-mRNA pairs were not restricted by their expression pattern.…”