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

Biochemical and Biophysical Research Communications
Qing ZhouZhi-Jun Chen

Abstract

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.

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