LncRNA HOTAIR regulates the lipid accumulation in non-alcoholic fatty liver disease via miR-130b-3p/ROCK1 axis
LncRNA HOTAIR regulates the lipid accumulation in non-alcoholic fatty liver disease via miR-130b-3p/ROCK1 axis
复制标题
LncRNA HOTAIR 通过 miR-130b-3p/ROCK1 轴调节非酒精性脂肪肝中的脂质积累
DOI：
10.1016/j.cellsig.2021.110190
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发表时间：
2022-02-01
影响因子：
4.8
通讯作者：
Chen, Hong
中科院分区：
文献类型：
--
作者：
Guo, Bo;Cheng, Yanzhen;Chen, Hong
背景：过度的肝脏脂质积累可导致非酒精性脂肪性肝病的发生。先前的研究表明，上调lncRNA HOTAIR可显著增加总胆固醇和甘油三酯。然而，HOTAIR在NAFLD进展过程中脂质积累中的作用尚不清楚。方法：采用高脂饮食模拟体内NAFLD，采用游离脂肪酸建立体外NAFLD模型。油红O染色检测脂肪堆积情况。H&E染色观察小鼠的病理变化。Western blot和qRT-PCR分别检测蛋白和mRNA水平。采用RIP检测HOTAIR、miR-130b-3p和ROCK1之间的关系。结果：NAFLD患者HOTAIR水平上调。HOTAIR的下调逆转了ffa处理的HepG2细胞和原代肝细胞的脂质积累。同时，HOTAIR与miR-130b-3p结合，ROCK1被鉴定为miR-130b-3p的直接靶点。此外，miR-130b-3p模拟物引起的脂质堆积减少被pcDNA3.1-ROCK1逆转。此外，miR-130b-3p模拟物对pAMPK2 α和ROCK1水平的影响被ROCK1过表达部分逆转。结论：HOTAIR的下调通过介导miR130b-3p/ROCK1轴显著抑制NAFLD的进展。我们的研究可能为探索治疗NAFLD的新方法提供新的思路。
Background: Excessive hepatic lipid accumulation can lead to the occurrence of non-alcoholic fatty liver disease. Previous study showed that upregulation of lncRNA HOTAIR significantly increased total cholesterol and triglyceride. However, the function of HOTAIR in lipid accumulation during the progression NAFLD remains unclear. Methods: High fat diet was used to mimic NAFLD in vivo, and free fatty acid was used to establish in vitro model of NAFLD. Oil red O staining was applied to test the lipid accumulation. The pathological changes in mice were observed by H&E staining. Western blot and qRT-PCR were applied to assess protein and mRNA levels, respectively. RIP assay was used to explore the relationship among HOTAIR, miR-130b-3p and ROCK1. Results: The level of HOTAIR was upregulated in NAFLD. Downregulation of HOTAIR reversed lipid accumulation in FFA-treated HepG2 cells and primary hepatocytes. Meanwhile, HOTAIR bound with miR-130b-3p, and ROCK1 was identified to be the direct target of miR-130b-3p. Moreover, miR-130b-3p mimics-caused lipid accumulation decrease was reversed by pcDNA3.1-ROCK1. Furthermore, the effect of miR-130b-3p mimics on pAMPK2 alpha and ROCK1 level was partially reversed by ROCK1 overexpression.Conclusion: Knockdown of HOTAIR significantly inhibited the progression of NAFLD through mediation of miR130b-3p/ROCK1 axis. Our study might shed new lights on exploring new methods against NAFLD.