Knockdown of HOTAIR Alleviates High Glucose-Induced Apoptosis and Inflammation in Retinal Pigment Epithelial Cells

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-alpha 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.