lncRNA HAND2-AS1对子痫前期患者血管内皮细胞的影响

Effects of incRNA HAND2-AS1 on vascular endothelial cells in preeclampsia patients

目的:探究lncRNA HAND反义RNA1(HAND2-AS1)、miRNA hsa-miR-520c-3p和整合素亚基β8(integrin subunit beta8,ITGB8)在子痫前期患者胎盘中表达量的改变以及HAND2-AS1对血管内皮功能的影响和机制。方法:收集25例子痫前期患者胎盘样本和20例匹配的健康产妇胎盘样本,通过荧光定量PCR技术检测HAND2-AS1、hsa-miR-520c-3p和ITGB8的表达量。通过细胞活力、划痕、血管形成和荧光定量PCR实验,观察过表达和敲低HAND2-AS1对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)增殖、迁移和血管形成的影响以及对hsa-miR-520c-3p和ITGB8表达量的影响。结果:与对照组胎盘相比,子痫前期患者胎盘中HAND2-AS1和ITGB8的表达量显著升高,而hsa-miR-520c-3p表达量降低。同时,子痫前期患者的胎盘中,HAND2-AS1的表达量与hsa-miR-520c-3p呈负相关,与ITGB8呈正相关。在HUVEC中过表达HAND2-AS1,HUVEC的增殖、迁移和血管形成能力减弱,同时hsa-miR-520c-3p表达量下降,ITGB8表达增高;敲低HAND2-AS1,结果相反。结论:HAND2-AS1抑制血管内皮增殖、迁移和血管形成能力,其潜在机制可能是通过调控hsa-miR-520c-3p/ITGB8的表达,有望成为子痫前期的治疗靶点。

Objective:This study aims to investigate the expression patterns of lncRNA HAND2-AS1,miRNA hsa-miR-520 c-3 p and integrin subunit beta 8(ITGB8)in placentas of preeclampsia(PE)patients and the role of HAND2-AS1 played in modulating vascular endothelial cells.Methods:Total 25 placentas of PE patients and 20 placentas of healthy controls were collected to detect the expressing abundance of HAND2-AS1,hsa-miR-520 c-3 p and ITGB8 using qRT-PCR technology.Proliferation,migration and angiogenesis of human umbilical vein endothelial cell(HUVEC)was detected through cell viability assay,wound healing assay and tube formation assay,respectively,when HAND2-AS1 was overexpressed or knock-down.Also,expression of hsa-miR-520 c-3 p and ITGB8 was detected using QPCR.Results:Compared with healthy controls,expression of HAND2-AS1 and ITGB8 increased and expression of hsa-miR-520 c-3 p decreased significantly in placentas of PE patients.In placentas of PE patients,the expression of HAND2-AS1 was negatively correlated with hsa-miR-520 c-3 p and positively correlated with ITGB8.The proliferation,migration and angiogenesis of HUVEC were impaired,the expression of hsa-miR-520 c-3 p decreased and the expression of ITGB8 increased when HAND2-AS1 was overexpressed.The result was the opposite when HAND2-AS1 was knocked-down.Conclusion:HAND2-AS1 inhibits proliferation,migration and angiogenesis of vascular endothelial cells,of which potential mechanism may be modulating expression of hsamiR-520 c-3 p/ITGB8.