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RSS FeedsIJMS, Vol. 20, Pages 6313: Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy (International Journal of Molecular Sciences)

 
 

13 december 2019 18:01:46

 
IJMS, Vol. 20, Pages 6313: Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy (International Journal of Molecular Sciences)
 


The aim of the study was to demonstrate how transthyretin (TTR) could affect long non-coding RNA (lncRNA) of maternally expressed gene 3 (MEG3) and play important roles in diabetic retinopathy (DR). A DR model in C57BL/6 mice was established after intraperitoneal injection of streptozotocin (STZ). After intravitreal injection with TTR pAAV vector, MEG3 short hairpin RNA (shRNA), scrambled shRNA, or MEG3, retinal imaging, retinal trypsin digestion, and fundus vascular permeability tests were performed. Cell counting kit-8 (CCK8), transwell, and Matrigel assays were employed to detect the proliferation and migration of human retinal microvascular endothelial cells (hRECs). The binding between long non-coding RNA of maternally expressed gene 3 (lncRNA-MEG3) and microRNA-223-3p (miR-223-3p) was observed by using luciferase reporter assays, while co-immunoprecipitation (co-IP) was employed to confirm the interaction between TTR and the target. In the DR mice model, retinal vascular leakage and angiogenesis were repressed by overexpressing TTR. In vitro, the added TTR promoted the level of lncRNA-MEG3 by interacting with poly (A) binding protein cytoplasmic 1 (PABPC1), and then repressed proliferation and angiogenesis of hRECs. In vivo, silencing or overexpressing lncRNA-MEG3 significantly affected retinal vascular phenotypes. Additionally, the interaction between lncRNA-MEG3 and miR-223-3p was confirmed, and silencing of miR-223-3p revealed similar effects on hRECs as overexpression of lncRNA-MEG3. In description, in the DR environment, TTR might affect the lncRNA MEG3/miR-223-3p axis by the direct binding with PABPC1, and finally repress retinal vessel proliferation.


 
43 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
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