■静脉畸形是最常见的先天性血管畸形,表现为局部侵袭和终身进行性发育的特征。长链非编码RNA(lncRNA)调节内皮细胞,血管平滑肌细胞,巨噬细胞,血管炎症,和新陈代谢,也影响静脉畸形的发展。本研究旨在阐明lncRNALEF1-AS1在静脉畸形发展中的作用,并检查LEF1-AS1,miR-489-3p,和HUVEC细胞中的S100A11。
■静脉畸形组织,相应的正常静脉组织,使用HUVEC细胞。Agilent人lncRNA微阵列基因芯片用于筛选差异基因,使用定量逆转录PCR检测RNA表达,蛋白质印迹法检测蛋白质表达。扩散,迁移,使用CCK8,transwell,和体外血管生成测试。
■使用基因芯片分析筛选了总共1,651个lncRNAs,其中1015例上调,636例下调。lncRNALEF1-AS1上调,差异有显著性,倍数变化值为11.03273。使用StarBase生物信息学预测网站进行的分析结果显示,LEF1-AS1和miR-489-3p具有互补的结合位点,并且miR-489-3p和S100A11也具有互补的结合位点。组织实验结果表明,LEF1-AS1和S100A11在静脉畸形组织中的表达高于正常组织,而miR-489-3p在静脉畸形中的表达低于正常组织。细胞培养实验表明LEF1-AS1促进细胞增殖,迁移,和HUVEC细胞的血管生成。在这些细胞中,LEF1-AS1靶向miR-489-3p,它又以S100A11为目标。LEF1-AS1作为竞争性内源性RNA,通过竞争性结合miR-489-3p促进S100A11的表达并促进增殖,迁移,和HUVEC细胞的血管生成。因此,LEF1-AS1参与了静脉畸形的发生发展。
■在静脉畸形中LEF1-AS1的表达上调,通过miR-489-3p对静脉内皮细胞的吸附,S100A11的表达增加,从而增强了扩散,迁移,和HUVEC细胞的血管生成。总之,LEF1-AS1通过调控miR-489-3p/S100A11轴参与静脉畸形的发生发展,这为该病的发病机制提供了宝贵的见解,并为其治疗开辟了新的途径。
UNASSIGNED: The venous malformation is the most common congenital vascular malformation and exhibits the characteristics of local invasion and lifelong progressive development. Long noncoding RNA (lncRNA) regulates endothelial cells, vascular smooth muscle cells, macrophages, vascular inflammation, and metabolism and also affects the development of venous malformations. This study aimed to elucidate the role of the lncRNA LEF1-AS1 in the development of venous malformations and examine the interaction among LEF1-AS1, miR-489-3p, and
S100A11 in HUVEC cells.
UNASSIGNED: Venous malformation tissues, corresponding normal venous tissues, and HUVEC cells were used. Agilent human lncRNA microarray gene chip was used to screen differential genes, RNA expression was detected using quantitative reverse transcription PCR, and protein expression was detected using Western blotting. The proliferation, migration, and angiogenesis of HUVEC cells were assessed using CCK8, transwell, and in vitro angiogenesis tests.
UNASSIGNED: A total of 1,651 lncRNAs were screened using gene chip analysis, of which 1015 were upregulated and 636 were downregulated. The lncRNA LEF1-AS1 was upregulated with an obvious difference multiple, and the fold-change value was 11.03273. The results of the analysis performed using the StarBase bioinformatics prediction website showed that LEF1-AS1 and miR-489-3p possessed complementary binding sites and that miR-489-3p and S100A11 also had complementary binding sites. The findings of tissue experiments revealed that the expressions of LEF1-AS1 and
S100A11 were higher in tissues with venous malformations than in normal tissues, whereas the expression of miR-489-3p was lower in venous malformations than in normal tissues. Cell culture experiments indicated that LEF1-AS1 promoted the proliferation, migration, and angiogenesis of HUVEC cells. In these cells, LEF1-AS1 targeted miR-489-3p, which in turn targeted
S100A11. LEF1-AS1 acted as a competitive endogenous RNA and promoted the expression of
S100A11 by competitively binding to miR-489-3p and enhancing the proliferation, migration, and angiogenesis of HUVEC cells. Thus, LEF1-AS1 participated in the occurrence and development of venous malformation.
UNASSIGNED: The expression of LEF1-AS1 was upregulated in venous malformations, and the expression of S100A11 was increased by the adsorption of miR-489-3p to venous endothelial cells, thus enhancing the proliferation, migration, and angiogenesis of HUVEC cells. In conclusion, LEF1-AS1 is involved in the occurrence and development of venous malformations by regulating the miR-489-3p/
S100A11 axis, which provides valuable insights into the pathogenesis of this disease and opens new avenues for its treatment.