Long noncoding RNA SNHG7 inhibits high glucose-induced human retinal endothelial cells angiogenesis by regulating miR-543/SIRT1 axis.

Diabetic retinopathy (DR) is the serious complication of type 2 diabetes mellitus, which could lead to visual impairment. Growing evidence have revealed the involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of DR. Thus, this study was performed to investigate the role of lncRNA SNHG7 (small nucleolar RNA host gene 7) in high glucose (HG)-induced proliferation, migration, and angiogenesis of human retinal endothelial cells (hRECs). We discovered that SNHG7 was decreased in hRECs under HG stimuli. Although SNHG7 had no influence on cell viability, migration and angiogenesis under condition, overexpression of SNHG7 inhibited the HG-induced cell proliferation, migration and angiogenesis, as well as vascular endothelial growth factor (VEGF) expression in HG condition. In terms of mechanism, we found that SNHG7 directly inhibited miR-543, which targeted the 3'-UTR of Silent information regulator T1 (SIRT1) mRNA and subsequently downregulated the VEGF expression in hRECs. Ultimately, upregulation of miR-543 or inhibition of SIRT1 both abrogated the effect of SNHG7 on HG-induced angiogenesis. Collectively, our results suggested that SNHG7 is a potential molecular target for attenuating HG-induced angiogenesis in the DR through regulation of the miR-543-mediated SIRT1/VEGF pathway.

Ke N ，Pi LH ，Liu Q ，Chen L ... -  《-》

MSC-derived exosomal lncRNA SNHG7 suppresses endothelial-mesenchymal transition and tube formation in diabetic retinopathy via miR-34a-5p/XBP1 axis.

Diabetic retinopathy (DR) is the most common complication of type 2 diabetes mellitus, which could result in visual impairment. Accumulating studies have shown the implication of long non-coding RNAs (lncRNAs) in the pathogenesis of DR. Our aims are to investigate whether lncRNA SNHG7 plays a role during DR pathogenesis. Human retinal microvascular endothelial cells (HRMECs) were treated with high glucose (HG) to build cell model. Relative expression of RNAs were examined using qPCR, and western blot or immunofluorescence analysis was adopted to detect the protein expression. Cell viability, migration and angiogenic capacity of HRMECs were estimated through CCK-8, transwell and tube formation experiments, respectively. Dual-luciferase reporter and RNA pull down assays were employed to verify the interplay between miR-34a-5p and SNHG7 or XBP1. Mesenchymal stem cells (MSCs) were identified by examining typical surface makers using flow cytometry and the differentiation abilities via Alizarin red, Oil red O and Alcian blue staining. MSC-derived exosomes were verified by transmission electron microscopy and western blot. LncRNA SNHG7 sponged to and negatively regulated miR-34a-5p. SNHG7 overexpression repressed HG induced endothelial-mesenchymal transition (EndMT) and tube formation of HRMECs, while miR-34a-5p overexpression could reverse this effect. miR-34a-5p targeted and negative regulated XBP1. Knockdown of miR-34a-5p repressed HG induced EndMT and tube formation, which were partially blocked by XBP1 inhibition. MSC-derived exosomes could transfer SNHG7 to HRMECs and modulated EndMT and tube formation. The MSC-derived exosomal lncRNA SNHG7 suppresses EndMT and tube formation in HRMECs via miR-34a-5p/XBP1 axis.

Cao X ，Xue LD ，Di Y ，Li T ，Tian YJ ，Song Y ... -  《-》

LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b/VE-cadherin axis.

Background: Diabetic retinopathy (DR) is currently the leading cause of blindness and visual disability in adults with diabetes mellitus (DM). Neovascularization has been identified as an important clinical property in DR, however, the exact mechanisms in DR neovascularization are still unclear and need further elucidation.Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of long non-coding RNA (lncRNA)-metastasis associated lung adenocarcinoma transcript 1 (MALAT1), miR-125b and vascular endothelial-cadherin (VE-cadherin) in human retina microvascular endothelial cells (hRMECs) treated with high glucose (HG). Luciferase assay was used to detect interaction of MALAT1 with miR-125b and miR-125b with VE-cadherin. MTT assay, transwell assay, tube formation assay and vascular permeability assay were conducted to detect the cell viability, migration tube formation ability and permeability of hRMECs, respectively. ELISA was used to examine the release of VE-cadherin and vascular endothelial growth factor (VEGF). Western blotting was used to access the protein expression of VE-cadherin, VEGF, β-catenin, matrix metalloproteinase (MMP) 2 (MMP2) and MMP9.Results: MALAT1 and VE-cadherin were up-regulated while miR-125b was down-regulated in hRMECs treated with HG. MALAT1 could competitively bind to miR-125b against VE-cadherin at the site of 3'-untranslated region (3'-UTR), leading to the up-regulation of VE-cadherin. Knockdown of MALAT1 inhibited the proliferation, migration, tube formation and vascular permeability of hRMECs induced by HG through up-regulating miR-125b. Furthermore, we found the deletion of MALAT1 suppressed the VE-cadherin/β-catenin complex and neovascularization related proteins expression, which was up-regulated by HG.Conclusion: Knockdown of MALAT1 inhibited cell proliferation, migration and angiogenesis of hRMECs via suppressing the VE-cadherin/β-catenin complex through targeting miR-125b. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for DR.

Liu P ，Jia SB ，Shi JM ，Li WJ ，Tang LS ，Zhu XH ，Tong P ... -  《-》

Transcriptome analysis identified a novel 3-LncRNA regulatory network of transthyretin attenuating glucose induced hRECs dysfunction in diabetic retinopathy.

Shao J ，Zhang Y ，Fan G ，Xin Y ，Yao Y ... -  《BMC Medical Genomics》

Knockdown of Malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis.

Diabetic retinopathy (DR), characterized by intraretinal vessel formation, is a major complication in diabetes. Neovascularization is an important characteristic of DR, but its formation mechanism remains unclear. In this research, Malat1, miR-205-5p, and VEGF-A levels in high glucose (HG) treat-human retinal microvascular endothelial cells (hRMECs) was detected with qRT-PCR. CCK-8 assay, transwell assay, and tube formation assay was applied to access hRMEC viability, migration, and angiogenesis. Expression level of endothelial-mesenchymal transition (EndMT) markers (VE-cadherin, FSP1, and α-SMA) was detected by western blotting assay. Interaction among Malat1, miR-205-5p, and VEGF-A was confirmed by dual-luciferase reporter assay. Furthermore, in vivo DR mouse model was induced, and the effect of Malat1 on DR and EndMT markers was confirmed through hematoxylin-eosin (HE) staining and western blotting. As a result, Malat1 and VEGF-A was upregulated while miR-205-5p was suppressed under HG conditions. Malat1 could sponge miR-205-5p to regulate VEGF-A expression. Malat1 knockdown inhibited hRMEC proliferation, migration, and tube formation by targeting miR-205-5p under HG conditions. Furthermore, inhibition of Malat1 prevented the HG-induced EndMT process. In summary, Malat1 knockdown diminished hRMEC dysfunctions by regulating miR-205-5p/VEGF-A, providing a useful insight for exploring new therapeutic target for DR.

Tan A ，Li T ，Ruan L ，Yang J ，Luo Y ，Li L ，Wu X ... -  《-》