Emergency Department, The Third Xiangya Hospital, Central South University, Changsha, China.
J Cell Physiol. 2020 Dec;235(12):9819-9833. doi: 10.1002/jcp.29795. Epub 2020 May 15.
Nonalcoholic fatty liver disease (NAFLD) is regarded as a threat to public health; however, the pathologic mechanism of NAFLD is not fully understood. We attempted to identify abnormally expressed long noncoding RNA (lncRNAs) and messenger RNA that may affect the occurrence and development of NAFLD in this study. The expression of differentially expressed lncRNAs in NAFLD was determined in oleic acid (OA)-treated L02 cells, and the functions of CCAT1 in lipid droplet formation were evaluated in vitro. Differentially expressed genes (DEGs) were analyzed by microarray analysis, and DEGs related to CCTA1 were selected and verified by weighted correlation network analysis. The dynamic effects of LXRα and CCTA1 on lipid droplet formation and predicted binding was examined. The binding between miR-631 and CCAT1 and LXRα was verified. The dynamic effects of miR-613 inhibition and CCTA1 silencing on lipid droplet formation were examined. The expression and correlations of miR-631, CCAT1, and LXRα were determined in tissue samples. As the results show, CCAT1 was induced by OA and upregulated in NAFLD clinical samples. CCAT1 silencing significantly suppressed lipid droplet accumulation in vitro. LXRα was positively correlated with CCAT1. By inhibiting miR-613, CCAT1 increased the transcription of LXRα and promoted LXRα expression. The expression of LXRα was significantly increased in NAFLD tissues and was positively correlated with CCAT1. In conclusion, CCAT1 increases LXRα transcription by serving as a competing endogenous RNA for miR-613 in an LXRE-dependent manner, thereby promoting lipid droplet formation and NAFLD. CCAT1 and LXRα might be potent targets for NAFLD treatment.
非酒精性脂肪性肝病（NAFLD）被认为是对公众健康的威胁；然而，NAFLD 的病理机制尚未完全阐明。在本研究中，我们试图鉴定可能影响 NAFLD 发生和发展的异常表达的长非编码 RNA（lncRNA）和信使 RNA。在油酸（OA）处理的 L02 细胞中测定 NAFLD 中差异表达的 lncRNA 的表达，并在体外评估 CCAT1 在脂滴形成中的功能。通过微阵列分析分析差异表达基因（DEGs），并通过加权相关网络分析选择和验证与 CCTA1 相关的 DEGs。检验 LXRα 和 CCTA1 对脂滴形成和预测结合的动态影响。验证 miR-631 和 CCAT1 与 LXRα 之间的结合。检验 miR-613 抑制和 CCTA1 沉默对脂滴形成的动态影响。检测组织样本中 miR-631、CCAT1 和 LXRα 的表达和相关性。结果表明，OA 诱导 CCAT1 表达，并在 NAFLD 临床样本中上调。CCAT1 沉默显著抑制体外脂滴积累。LXRα 与 CCAT1 呈正相关。通过抑制 miR-613，CCAT1 增加 LXRα 的转录并促进 LXRα 表达。LXRα 在 NAFLD 组织中的表达显著增加，并与 CCAT1 呈正相关。总之，CCAT1 通过作为 miR-613 的竞争性内源性 RNA，以 LXRE 依赖的方式增加 LXRα 的转录，从而促进脂滴形成和 NAFLD。CCAT1 和 LXRα 可能是治疗 NAFLD 的有效靶点。
