Wu Yanping, Liang Zenghui, Li Kun, Feng Junli
Department of Pediatric Ophthalmology, Cangzhou Central Hospital, No. 16, Xinhua West Street, Cangzhou, 061000, Hebei Province, China.
Department of Interventional Medicine, Cangzhou People's Hospital, Cangzhou, China.
Appl Biochem Biotechnol. 2025 Mar;197(3):1743-1759. doi: 10.1007/s12010-024-05083-2. Epub 2024 Nov 28.
Diabetic retinopathy (DR) is one of the most common microvascular complications in diabetes. Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) played critical regulatory roles in DR. However, the role of lncRNA HOX Transcript Antisense Intergenic RNA (HOTAIR) in the high glucose (HG)-induced human retinal pigment epithelial (RPE) cell injury remains unclear. Herein, we found the expression of HOTAIR was increased in the retina of DR rats and HG-induced ARPE-19 cells. Knockdown of HOTAIR improved viability, inhibited apoptosis, increased Bcl-2 protein levels, and decreased Bax and cleaved caspase 3 protein levels in HG-treated ARPE-19 cells. Moreover, enzyme-linked immunosorbent assay showed that HOTAIR silencing reduced interleukin 6 and tumor necrosis factor-α release of ARPE-19 cells under HG conditions. Mechanistically, luciferase reporter assay and RNA immunoprecipitation assay validated that HOTAIR could directly sponge miR-326 to upregulate transcription factor 4 (TCF4) expression. Furthermore, rescue experiments confirmed that HOTAIR promoted apoptosis and inflammation of HG-treated ARPE-19 cells by the miR-326/TCF4 axis. In summary, HOTAIR enhanced HG-induced retinal pigment epithelial cell injury by promoting apoptosis and inflammation, shedding light on the importance of HOTAIR as a novel potential target for DR treatment.
糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症之一。越来越多的证据表明，长链非编码RNA（lncRNA）在DR中发挥着关键的调节作用。然而，lncRNA HOX转录反义基因间RNA（HOTAIR）在高糖（HG）诱导的人视网膜色素上皮（RPE）细胞损伤中的作用仍不清楚。在此，我们发现DR大鼠视网膜和HG诱导的ARPE-19细胞中HOTAIR的表达增加。敲低HOTAIR可提高HG处理的ARPE-19细胞的活力，抑制细胞凋亡，增加Bcl-2蛋白水平，并降低Bax和裂解的caspase 3蛋白水平。此外，酶联免疫吸附测定表明，HOTAIR沉默可降低HG条件下ARPE-19细胞白细胞介素6和肿瘤坏死因子-α的释放。机制上，荧光素酶报告基因测定和RNA免疫沉淀测定证实，HOTAIR可直接吸附miR-326以上调转录因子4（TCF4）的表达。此外，挽救实验证实，HOTAIR通过miR-326/TCF4轴促进HG处理的ARPE-19细胞的凋亡和炎症。总之，HOTAIR通过促进凋亡和炎症增强了HG诱导的视网膜色素上皮细胞损伤，为HOTAIR作为DR治疗的新型潜在靶点的重要性提供了线索。
