期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 235, 期 11, 页码 8270-8282出版社
WILEY
DOI: 10.1002/jcp.29483
关键词
circular RNA; hepatic stellate cell; miRNA sponge; radiation-induced liver disease
资金
- National Natural Science Foundation of China [81773220, 81903132]
- President Foundation of Nanfang Hospital, Southern Medical University [2018C001]
- Natural Science Foundation of Guangdong Province [2019A1515011652]
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 alpha-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.
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