Knockdown of lncRNA TUG1 suppresses corneal angiogenesis through regulating miR-505-3p/VEGFA.

Vascular endothelial growth factor A (VEGFA) is one of the major factors initiating and regulating angiogenesis. LncRNA taurine up-regulated gene 1 (TUG1) has been implicated in the pathological neovascularization. The aim of this study is to explore the function of TUG1 in regulating VEGFA-mediated angiogenesis in endothelial cells. A total of 12 corneal neovascularization (CRNV) samples were collected form patient undergoing corneal transplantation at Tongji Hospital, Wuhan, China. qRT-PCR and Western blotting were performed to examine gene expression and protein levels. Human umbilical vein endothelial cells (HUVECs) were used as an in vitro angiogenesis model. CCK-8 proliferation assay was used to determine cell proliferation capacity and wound healing was performed to analyze cell migration ability. Dual luciferase reporter assay was used for functional interaction validation between miR-505-3p and its targets. The in vitro angiogenic potential was evaluated by tube formation assay. TUG1 and VEGFA were upregulated in CRNV tissues and VEGFA-treated HUVECs. TUG1 knockdown inhibited proliferation, migration and tube formation capacity of HUVECs. TUG1 regulated the angiogenesis of HUVECs by modulating VEGFA expression through targeting miR-505-3p. Our results suggest that lncRNA TUG1 promotes the angiogenesis of HUVECs through modulating miR-505-3p/VEGFA axis.

Liu S ，Gao J ，Chen J 《-》

Long noncoding TUG1 promotes angiogenesis of HUVECs in PE via regulating the miR-29a-3p/VEGFA and Ang2/Tie2 pathways.

Preeclampsia (PE) is a pregnancy-specific disease that is associated with oxidative stress-induced endothelial dysfunction. Long noncoding RNAs (lncRNAs) are related to PE progression. The purpose is to study whether lncRNA taurine-upregulated gene 1 (TUG1) takes part in endothelial dysfunction in PE. The placenta tissues were collected from PE patients and normal subjects. Human umbilical vein endothelial cells (HUVECs) were suffered from hypoxia-reoxygenation (H/R). TUG1, miR-29a-3p and vascular endothelial growth factor A (VEGFA) were detected via qRT-PCR. soluble fms-related tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG) levels were detected by ELISA. Cell proliferation, migration, invasion and angiogenesis were examined via MTT, wound healing analysis, transwell and tube formation analysis. The proteins in VEGFA and angiopoietin 2 (Ang2)/tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) signaling were measured by western blot. The binding relationship was analyzed via Starbase, Jefferson and dual-luciferase reporter analysis. TUG1 and VEGFA levels were downregulated, and levels of miR-29a-3p, sFLT1 and sENG were increased in PE patients. TUG1 abundance was reduced in H/R-stimulated HUVECs, and TUG1 overexpression increased proliferation, migration, invasion and angiogenesis, and activated the VEGFA and Ang2/Tie2 signaling in H/R-stimulated HUVECs. TUG1 sponged miR-29a-3p, and miR-29a-3p overexpression reversed the function of TUG1 on H/R-induced HUVECs dysfunction. MiR-29a-3p knockdown attenuated H/R-induced inhibition of proliferation, migration, invasion, angiogenesis and activation of the VEGFA and Ang2/Tie2 signaling in HUVECs. VEGFA and Ang2 were targeted by miR-29a-3p, and VEGFA or Ang2 silence weakened the role of miR-29a-3p knockdown in H/R-caused HUVECs dysfunction. TUG1 facilitates proliferation, migration, invasion and angiogenesis in H/R-stimulated HUVECs via activating the VEGFA and Ang2/Tie2 signaling by regulating miR-29a-3p.

Liu Z ，Guo N ，Zhang XJ 《-》

Long noncoding RNA TUG1 upregulates VEGFA to enhance malignant behaviors in stomach adenocarcinoma by sponging miR-29c-3p.

Long noncoding RNA (lncRNA) TUG1 has been reported to display a pivotal role in the tumorigenesis and malignant progression of various types of cancers, including stomach adenocarcinoma (STAD). However, the contribution of aberrant expression of TUG1 and the mechanism by which it serves as a competing endogenous RNA (ceRNA) in STAD remains largely obscure. The human STAD cell lines (MGC-803 and AGS), human normal gastric epithelial cell line (GES-1), human umbilical vein endothelial cells (HUVECs), and human embryonic kidney cells (HEK293T) were purchased and cultured to investigate the roles of TUG1 in STAD. Twenty BALB/c nude mice were purchased to establish a xenograft model to explore the roles of TUG1 in vivo. Bioinformatics analysis revealed that TUG1 was upregulated in STAD, of which expression was negatively and positively correlated with miR-29c-3p and VEGFA, respectively. Functional analyses indicated that TUG1 functioned as an oncogene to promote malignant behaviors (proliferation, migration, and angiogenesis) of STAD cells; whereas miR-29c-3p exerted the opposite role. Mechanistically, the interaction between miR-29c-3p with TUG1 and VEGFA was demonstrated. It was observed that miR-29c-3p could reverse the TUG1-induced promotion effect on cell proliferation, migration, and angiogenesis in STAD. Furthermore, TUG1 overexpression promoted STAD cell proliferation, metastasis, and angiogenesis, whereas VEGFA silence restored these effects, both in vitro and in vivo. This finding confirmed that lncRNA TUG1 acts as a ceRNA for miR-29c-3p to promote tumor progression and angiogenesis by upregulating VEGFA, indicating TUG1 as a therapeutic target in STAD management.

Jin Y ，Cao J ，Hu X ，Cheng H ... -  《-》

The long noncoding RNA PDK1-AS/miR-125b-5p/VEGFA axis modulates human dermal microvascular endothelial cell and human umbilical vein endothelial cell angiogenesis after thermal injury.

Our previous study confirmed the critical role of miR-125b and vascular endothelial growth factor (VEGF) in burn wound repair., The present study was aimed to identify the role of long noncoding RNAs (lncRNAs) related to the function of miR-125b and VEGF in burn wound repair and the underlying mechanism. First, we found that lncRNA PDK1-AS and VEGFA expression was significantly increased in heat-denatured dermal tissue samples and in human dermal microvascular endothelial cells (HDMECs) and human umbilical vein endothelial cells (HUVECs) after thermal injury. PDK1-AS knockdown significantly inhibited cell viability, cumulative tube length, cell migratory ability, and cell invasion of thermally injured HDMECs and HUVECs. PDK1-AS knockdown decreased VEGFA protein levels in HDMECs and HUVECs. While overexpression of PDK1-AS showed the opposite effects. Online tools prediction and luciferase assay confirmed that miR-125b-5p targeted PDK1-AS and VEGFA 3'-untranslated region. miR-125b-5p inhibition significantly increased VEGFA protein levels and enhanced viability, cumulative tube length, migratory ability, and invasion of HUVECs and HDMECs. Furthermore, the effects of PDK1-AS knockdown on VEGFA protein levels in the two cell lines were partially reversed by miR-125b-5p inhibition. Finally, in the tissue samples, PDK1-AS and VEGFA expression was increased, while miR-125b-5p expression was decreased in heat-denatured dermal tissues; the expression of miR-125b-5p had a negative correlation with PDK1-AS and VEGFA, respectively, and PDK1-AS and VEGFA were positively correlated with each other in tissue samples. In conclusion, PDK1-AS relieves miR-125b-5p-induced inhibition on VEGFA by acting as a endogenous RNA, therefore modulating HDMEC and HUVEC angiogenesis after thermal injury.

Zhou S ，Liang P ，Zhang P ，Zhang M ，Huang X ... -  《-》

lncRNA TUG1 regulates angiogenesis via the miR‑204‑5p/JAK2/STAT3 axis in hepatoblastoma.

Yuan MX ，Ji CY ，Gao HQ ，Sheng XY ，Xie WX ，Yin Q ... -  《-》