Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Ophthalmology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Department of Ophthalmology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):3134-3141. doi: 10.1016/j.bbrc.2018.08.105. Epub 2018 Aug 23.
Sustained retinal hypoxia causes injuries to retinal pigment epithelium (RPE) cells. We studied expression and potential functions of nuclear factor-κB (NFκB) Interacting LncRNA (NKILA) in hypoxia-treated RPE cells. Hypoxia induced NKILA expression, NKILA-IκBα association and NFκB activation in ARPE-19 cells and primary human RPE cells. shRNA-mediated knockdown of NKILA facilitated NFκB activation, inhibiting RPE cell death and apoptosis. Conversely, exogenous overexpression of NKILA blocked hypoxia-induced NFκB activation, thereby exacerbating RPE cell apoptosis. Further studies show that hypoxia downregulated microRNA-103 (miR-103), the anti-NKILA microRNA, in RPE cells. Transfection of miR-103 mimic blocked hypoxia-induced NKILA expression to significantly boost NFκB activation, protecting RPE cells from hypoxia. Collectively, we conclude that hypoxia-induced NKILA expression negatively regulates NFκB to promote RPE cell death. Conversely, NKILA inhibition protects RPE cells from hypoxia by facilitating NFκB activation.
持续性视网膜缺氧会导致视网膜色素上皮 (RPE) 细胞损伤。我们研究了核因子-κB (NFκB) 相互作用的长非编码 RNA (NKILA) 在缺氧处理的 RPE 细胞中的表达和潜在功能。缺氧诱导 ARPE-19 细胞和原代人 RPE 细胞中 NKILA 的表达、NKILA-IκBα 结合和 NFκB 激活。shRNA 介导的 NKILA 敲低促进了 NFκB 的激活，抑制了 RPE 细胞的死亡和凋亡。相反，外源性过表达 NKILA 阻断了缺氧诱导的 NFκB 激活，从而加重了 RPE 细胞的凋亡。进一步的研究表明，缺氧下调了 RPE 细胞中的 microRNA-103 (miR-103)，即 NKILA 的反义 microRNA。转染 miR-103 模拟物阻断了缺氧诱导的 NKILA 表达，从而显著增强了 NFκB 的激活，保护 RPE 细胞免受缺氧。总之，我们得出结论，缺氧诱导的 NKILA 表达通过负调控 NFκB 促进 RPE 细胞死亡。相反，NKILA 抑制通过促进 NFκB 激活来保护 RPE 细胞免受缺氧。
