Long non‐coding ribonucleic acid urothelial carcinoma‐associated 1 promotes high glucose‐induced human retinal endothelial cells angiogenesis through regulating micro‐ribonucleic acid‐624‐3p/vascular endothelial growth factor C

Abstract

Aims/Introduction Emerging evidence has indicated that long non‐coding ribonucleic acids play important roles in the development and progression of diabetic retinopathy (DR). It is reported that urothelial carcinoma‐associated 1 (UCA1) is highly expressed in diabetic lymphoendothelial cells and influences glucose metabolism in rats with DR. The aim of the present study was to explore the role of UCA1 in the mechanism of DR. Materials and Methods Gene expression analyses in fibrovascular membranes excised from patients with DR using public microarray datasets (GSE60436). Reverse transcription polymerase chain reaction was carried out to detect UCA1, micro‐ribonucleic acid (miR)‐624‐3p and vascular endothelial growth factor C (VEGF‐C) expressions in the blood of patients and human retinal endothelial cells (HRECs). Furthermore, Cell Counting kit‐8, Transwell assay, and tube formation assay were used to identify biological effects of UCA1 on HRECs proliferation, migration ability and angiogenesis in vitro. Results UCA1 and VEGF‐C were elevated in DR patients and high glucose‐induced HRECs cell lines, whereas miR‐624‐3p was decreased. UCA1 inhibition inhibited proliferation, angiogenesis and migration of HRECs cells under high‐glucose condition. Luciferase reporter assay showed that UCA1 could sponge with miR‐624‐3p, which could directly target VEGF‐C. Finally, we proved a pathway that UCA1 promoted cell proliferation, migration and angiogenesis through sponging with miR‐624‐3p, thereby upregulating VEGF‐C in high‐glucose‐induced HRECs. Conclusions We identified UCA1 as an important factor associated with DR, which could regulate the expression of VEGF‐C by sponging miR‐624‐3p in human retinal endothelial cells. Our results pave the way for further studies on diagnostic and therapeutic studies related to UCA1 in DR patients.

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

“…The most commonly used assays to evaluate in vitro angiogenesis are migration, proliferation, and tube formation assays of ECs in response to inhibitory or stimulatory compounds [ 27 ]. In this study, the migration and tube formation of HRMECs were investigated, and high-glucose treatment was found to significantly enhance the two steps of retinal angiogenesis, consistent with previous reports [ 28 , 29 ]. When ghrelin was used in combination with high-glucose treatment, the migration and tube formation abilities of HRMECs were weakened, and siGHSR-1a restored the promoting effects of high glucose on these two steps of angiogenesis.…”

Role of Lnc-RNAs in the Pathogenesis and Development of Diabetic Retinopathy

“…It was also shown that the expression levels of miR-624-3p were reduced, leading to cell proliferation, migration and angiogenesis by promoting VEGF-C expression in endothelial cells. In conclusion, UCA1 may act as a sponge of miR-624-3p to stimulate high-glucose-induced neovascularization [ 82 ].…”

Diabetic Retinopathy: Are lncRNAs New Molecular Players and Targets?

“…Particularly, in diabetic patients with DR or in human retinal endothelial cells cultured with HG concentrations, the upregulation of several different lncRNAs has been recently reported. Although further analyses are needed, for most of the mentioned lncRNAs, preliminary evidence suggests a putative role in DR. Of note, the in vitro knockdown of these lncRNAs ameliorates retinal dysfunctions improving various related-biological processes, such as proliferation, apoptosis, migration, angiogenesis, inflammation, or redox state [ 62 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 ]. For instance, ARPE-19 cells exposed to HG display increased expression of IGF2 Antisense RNA ( IGF2-AS ) and enhanced apoptosis, and IGF2-AS silencing restrains apoptosis, inducing IGF2/Akt signaling and reducing Casp-9 expression [ 114 ].…”

“…Particularly, Long Intergenic Non-Coding RNA 174 ( LINC00174 ) is able to bind miR-150-5p, which targets the untranslated 3′ region of VEGFA [ 120 ], whereas Taurine-Upregulated Gene 1 ( TUG1 ) also prevents VEGF A suppression by the interaction with miR-145 [ 121 ]. Similarly, Urothelial Carcinoma-Associated 1 ( UCA1 ) lncRNA could sponge miR-624-3p regulating the expression of VEGF-C [ 122 ]. Moreover, the Long Intergenic Non-Coding RNA 963 ( LINC00963 ) may regulate the proliferation and apoptosis in HG-induced HERCs by directly targeting miR-27b [ 123 ].…”