Chen Xue, Sun Ruxu, Yang Daidi, Jiang Chao, Liu Qinghuai
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210029, China.
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210029, China.
Mol Ther Nucleic Acids. 2020 Mar 6;19:1015-1026. doi: 10.1016/j.omtn.2019.12.040. Epub 2020 Jan 15.
Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play significant roles in various diseases; however, their roles in age-related macular degeneration (AMD) remain unclear. Dedifferentiation and dysfunction of retinal pigment epithelium (RPE) cells have been shown to contribute to AMD etiology in several studies. Herein, we found that lncRNA LINC00167 was downregulated in RPE-choroid samples of AMD patients and dysfunctional RPE cells, and it was consistently upregulated along with RPE differentiation. In vitro study indicated that reduced endogenous LINC00167 expression resulted in RPE dedifferentiation, which was typified by attenuated expression of RPE markers, reduced vascular endothelial growth factor A secretion, accumulation of mitochondrial reactive oxygen species, and interrupted phagocytic ability. Mechanistically, LINC00167 functioned as a sponge for microRNA miR-203a-3p to restore the expression of the suppressor of cytokine signaling 3 (SOCS3), which further inhibited the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Taken together, our study demonstrated that LINC00167 showed a protective role in AMD by maintaining RPE differentiation through the LINC00167/miR-203a-3p/SOCS3 axis and might be a potential therapeutic target for AMD.
越来越多的证据表明，长链非编码RNA（lncRNA）在各种疾病中发挥着重要作用；然而，它们在年龄相关性黄斑变性（AMD）中的作用仍不清楚。多项研究表明，视网膜色素上皮（RPE）细胞的去分化和功能障碍与AMD的病因有关。在此，我们发现lncRNA LINC00167在AMD患者的RPE-脉络膜样本和功能失调的RPE细胞中表达下调，并且随着RPE分化其表达持续上调。体外研究表明，内源性LINC00167表达降低导致RPE去分化，其特征为RPE标志物表达减弱、血管内皮生长因子A分泌减少、线粒体活性氧积累以及吞噬能力中断。机制上，LINC00167作为微小RNA miR-203a-3p的海绵，以恢复细胞因子信号传导抑制因子3（SOCS3）的表达，进而抑制Janus激酶（JAK）/信号转导子和转录激活子（STAT）信号通路。综上所述，我们的研究表明，LINC00167通过LINC00167/miR-203a-3p/SOCS3轴维持RPE分化，在AMD中发挥保护作用，可能是AMD的潜在治疗靶点。
