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首页> 外文期刊>Journal of cellular physiology. >Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR-146a-5p
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Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR-146a-5p

机译：环状RNA RSF1促进炎症和辐照肝脏纤维化的表型星状细胞通过调节mir - 146 - 5 - p

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摘要

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, proinflam-matory cytokines production, and α-smooth muscle actin expression, which were blocked by microRNA (miR)-146a-5p mimics. CircRNA RSF1 (circRSFl) was upregu-lated 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 circRSFl and miR-146a-5p. Enforced expression of circRSFl 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 circRSFl, miR-146a-5p, and RAC1 in irradiated HSC, which may provide attractive therapeutic targets for RILD.
机译：环状RNA的作用(circRNA)辐射诱导肝脏疾病(RILD)仍然存在很大程度上是未知的。肉毒杆菌毒素基质1 (RAC1)升高在人类肝星状细胞(HSC)辐照行LX2,重要的效应细胞调停RILD。增殖,proinflam-matory细胞因子生产,α平滑肌肉肌动蛋白的表达,由微rna (miR) -146 a-5p阻塞模仿。在辐照LX2细胞并预测港口结合位点mir - 146 - a - 5 - p。下拉和dual-luciferase记者检测确认circRSFl的直接交互mir - 146 - 5 - p。作为增加RAC1表达式mir - 146 - 5 - p海绵抑制mir - 146 - 5 - p活动,从而增强细胞活力,促进炎症和纤维化的表型辐照LX2细胞。功能性监管轴组成circRSFl, mir - 146 - 5 - p和RAC1辐照HSC,提供有吸引力的治疗RILD的目标。

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