NKILA inhibition protects retinal pigment epithelium cells from hypoxia by facilitating NFκB activation

作者：Zhou, Qing; Zhou, Lu; Qian, Jing; Yuan, Zhi-lan^*; Chen, Zhi-jun^*

来源：Biochemical and Biophysical Research Communications, 2018, 503(4): 3134-3141.

DOI：10.1016/j.bbrc.2018.08.105

• Hypoxia
• Retinal pigment epithelium (RPE) cells
• NKILA
• NF kappa B
• microRNA-103

Sustained retinal hypoxia causes injuries to retinal pigment epithelium (RPE) cells. We studied expression and potential functions of nuclear factor-kappa B (NF kappa B) Interacting LncRNA (NKILA) in hypoxia-treated RPE cells. Hypoxia induced NKILA expression, NKILA-1 kappa B alpha association and NF kappa B activation in ARPE-19 cells and primary human RPE cells. shRNA-mediated knockdown of NKILA facilitated NF kappa B activation, inhibiting RPE cell death and apoptosis. Conversely, exogenous overexpression of NKILA blocked hypoxia-induced NF kappa B 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 NF kappa B activation, protecting RPE cells from hypoxia. Collectively, we conclude that hypoxia-induced NKILA expression negatively regulates NF kappa B to promote RPE cell death. Conversely, NKILA inhibition protects RPE cells from hypoxia by facilitating NF kappa B activation.

• 出版日期2018-9-18
• 单位南京医科大学