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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chen, Y; Yuan, B; Chen, G; Zhang, L; Zhuang, Y; Niu, H; Zeng, Z

Published Date

  • November 2020

Published In

Volume / Issue

  • 235 / 11

Start / End Page

  • 8270 - 8282

PubMed ID

  • 31960423

Electronic International Standard Serial Number (EISSN)

  • 1097-4652

Digital Object Identifier (DOI)

  • 10.1002/jcp.29483


  • eng

Conference Location

  • United States