Patients with chronic hyperglycemia are at high risk of developing diabetic retinopathy. In this study, we investigated the functional role of long-noncoding RNA (lncRNA) X-inactive specific transcript (XIST) in an in vitro model of diabetic hyperglycemia in human retinal pigment epithelial ARPE-19 cells.

ARPE-19 cells were cultured in normal glucose (NG) and high-glucose (HG) conditions to mimic hyperglycemia-associated cell apoptosis, migration and XIST expression. XIST was overexpressed in ARPE-19 cells to examine its functions in HG-induced cell apoptosis and migration. The downstream competing target of XIST, human mature microRNA-21-5p (hsa-miR-21-5p) was assessed by dual-luciferase assay and qRT-PCR. Hsa-miR-21-5p was upregulated in XIST-overexpressed ARPE-19 cells to further assess the functional correlation between XIST and hsa-miR-21-5p in hyperglycemia-associated cell apoptosis and migration.

HG insult increased apoptosis, reduced migration and downregulated XIST in ARPE-19 cells. XIST overexpression significantly protected HG insult in ARPE-19 cells, by reducing apoptosis and restoring migration capability. XIST directly bound and inhibited hsa-miR-21-5p expression in HG-insulted ARPE-19 cells. Furthermore, hsa-miR-21-5p upregulation reversed the protective effects of XIST in HG-insulted ARPE-19 cells.

XIST, likely through competitive binding of hsa-miR-21-5p, provides protection against hyperglycemia-associated injury in human retinal pigment epithelial cells.