Xiang Juan, Deng Yuan-Yuan, Liu Hui-Xia, Pu Ying
Endocrinology Subspecialty of Geriatrics, Xiangya Hospital of Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China.
Front Bioeng Biotechnol. 2022 Jun 13;10:858558. doi: 10.3389/fbioe.2022.858558. eCollection 2022.
Long non-coding RNAs (lncRNAs) are known to play crucial roles in nonalcoholic fatty liver disease (NAFLD). This research sought to explore mechanisms by which lncRNA MALAT1 regulates the progression of NAFLD. Thus, in order to detect the function of MALAT1 in NAFLD, and model of NAFLD were established. Then, fatty acid uptake and triglyceride level were investigated by BODIPY labeled-fatty acid uptake assay and Oil red O staining, respectively. The expressions of MALAT1, miR-206, ARNT, PPARα and CD36 were detected by western blotting and qPCR. Dual luciferase, RIP and ChIP assay were used to validate the relation among MALAT1, miR-206, ARNT and PPARα. The data revealed expression of MALAT1 was up-regulated and in NAFLD, and knockdown of MALAT1 suppressed FFA-induced lipid accumulation in hepatocytes. Meanwhile, MALAT1 upregulated the expression of ARNT through binding with miR-206. Moreover, miR-206 inhibitor reversed MALAT1 knockdown effects in decreased lipid accumulation in FFA-treated hepatocytes. Furthermore, ARNT could inhibit the expression of PPARα via binding with PPARα promoter. Knockdown of MALAT1 significantly upregulated the level of PPARα and downregulated the expression of CD36, while PPARα knockdown reversed these phenomena. MALAT1 regulated PPARα/CD36 -mediated hepatic lipid accumulation in NAFLD through regulation of miR-206/ARNT axis. Thus, MALAT1/miR-206/ARNT might serve as a therapeutic target against NAFLD.
已知长链非编码RNA（lncRNA）在非酒精性脂肪性肝病（NAFLD）中发挥关键作用。本研究旨在探索lncRNA MALAT1调节NAFLD进展的机制。因此，为了检测MALAT1在NAFLD中的功能，建立了NAFLD模型。然后，分别通过BODIPY标记的脂肪酸摄取试验和油红O染色研究脂肪酸摄取和甘油三酯水平。通过蛋白质免疫印迹法和定量聚合酶链反应检测MALAT1、miR-206、芳香烃受体核转运蛋白（ARNT）、过氧化物酶体增殖物激活受体α（PPARα）和脂肪酸转运蛋白CD36的表达。采用双荧光素酶报告基因检测、RNA免疫沉淀和染色质免疫沉淀试验验证MALAT1、miR-206、ARNT和PPARα之间的关系。数据显示，MALAT1在NAFLD中的表达上调，敲低MALAT1可抑制游离脂肪酸（FFA）诱导的肝细胞脂质积累。同时，MALAT1通过与miR-206结合上调ARNT的表达。此外，miR-206抑制剂可逆转MALAT1敲低对FFA处理的肝细胞脂质积累减少的影响。此外，ARNT可通过与PPARα启动子结合抑制PPARα的表达。敲低MALAT1可显著上调PPARα水平并下调CD36的表达，而敲低PPARα可逆转这些现象。MALAT1通过调节miR-206/ARNT轴调控PPARα/CD36介导的NAFLD肝脏脂质积累。因此，MALAT1/miR-206/ARNT可能成为治疗NAFLD的靶点。
