Background: As one of the most common liver disorders worldwide, nonalcoholic fatty liver disease (NAFLD) begins with the abnormal accumulation of triglyceride (TG) in the liver and can lead to inflammation and fibrosis. Long noncoding RNA (lncRNA) NEAT1 was reported to promote NAFLD progress. However, its molecular mechanism in NAFLD was not fully clear. Method: In vitro cellular model of NAFLD was established with BRL3A cell treated by free fatty acid (FFA). Cell Counting Kit-8 (CCK-8) assay was carried out to assess cell proliferation. The expression of mRNA and protein of inflammation and fibrosis in BRL3A cell was detected by qRT-PCR and Western blot. Bioinformatics and dual-luciferase reporter assays were used to predict and validate the interaction between NEAT1 and miR-506 as well as GLI3 and miR-506. Results: NEAT1 was upregulated while miR-506 was downregulated in the progression of NAFLD. Meanwhile, NEAT1 and miR-506 were proved to regulate fibrosis, inflammatory response, and lipid metabolism. Knockdown of NEAT1 inhibited GLI3 expression and promoted miR- 506 expression, Overexpression of miR-506 inhibited NEAT1 and GLI3 expression. Moreover, dual-luciferase reporter assays proved that miR-506 could bind to NEAT1 and GLI3, whereas NEAT1 could sponge miR-506 to regulate GLI3 expression. Conclusion: lncRNA NEAT1 could regulate fibrosis, inflammatory response, and lipid metabolism via the miR-506/GLI3 axis as a ceRNA, which is a novel mechanistic role in the regulation of NAFLD. These results provide a new potential treatment target for NAFLD.

中文翻译：

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lncRNA NEAT1通过调节miR-506 / GLI3来调节非酒精性脂肪肝引起的纤维化和炎症反应。

背景：作为全球最常见的肝脏疾病之一，非酒精性脂肪性肝病（NAFLD）始于肝脏中甘油三酸酯（TG）的异常蓄积，并可导致炎症和纤维化。据报道，长非编码RNA（lncRNA）NEAT1可以促进NAFLD进展。但是，其在NAFLD中的分子机制尚不完全清楚。方法：体外用游离脂肪酸（FFA）处理的BRL3A细胞建立了NAFLD的细胞模型。进行细胞计数试剂盒8（CCK-8）分析以评估细胞增殖。用qRT-PCR和Western blot检测BRL3A细胞炎症和纤维化mRNA和蛋白的表达。使用生物信息学和双重荧光素酶报告基因检测法预测和验证NEAT1和miR-506以及GLI3和miR-506之间的相互作用。结果：在NAFLD进展中，NEAT1上调而miR-506下调。同时，NEAT1和miR-506被证明可以调节纤维化，炎症反应和脂质代谢。抑制NEAT1抑制GLI3表达并促进miR-506表达，miR-506的过表达抑制NEAT1和GLI3表达。此外，双荧光素酶报告基因检测证明miR-506可以与NEAT1和GLI3结合，而NEAT1可以使miR-506调节GLI3的表达。结论： lncRNA NEAT1可以通过miR-506 / GLI3轴作为ceRNA调控纤维化，炎症反应和脂质代谢，这是NAFLD调控的新机制。这些结果为NAFLD提供了新的潜在治疗靶标。