Long non-coding RNA XIST regulates hyperglycemia-associated apoptosis and migration in human retinal pigment epithelial cells - 14/03/20

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Iconographies | 5 |
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Graphical abstract |
Highlights |
• | HG insult increased apoptosis and downregulated XIST in ARPE-19 cells. |
• | XIST overexpression significantly protected HG insult in ARPE-19 cells. |
• | XIST directly bound and inhibited hsa-miR-21-5p in HG-insulted ARPE-19 cells. |
• | Hsa-miR-21-5p upregulation reversed the protective effects of XIST in ARPE-19 cells. |
Abstract |
Objective |
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 anin vitro model of diabetic hyperglycemia in human retinal pigment epithelial ARPE-19 cells.
Method |
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.
Results |
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.
Conclusion |
XIST, likely through competitive binding of hsa-miR-21-5p, provides protection against hyperglycemia-associated injury in human retinal pigment epithelial cells.
Le texte complet de cet article est disponible en PDF.Keywords : Diabetic retinopathy, Hyperglycemia, Apoptosis, lncRNA, XIST, miRNA
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