长链非编码RNA尿路上皮癌相关因子1通过调控妊娠高血压患者的miR-197-3p/组蛋白去乙酰化酶-2轴，保护人胎盘血管内皮细胞免受缺氧诱导的损伤。
Long noncoding RNA urothelial carcinoma associated 1 protects human placental vascular endothelial cells from hypoxia-induced damage by regulating the miR-197-3p/histone deacetylase-2 axis in patients with pregnancy-induced hypertension.
作者信息
Li Jie, Lu Yiling, Wang Ying, Wang Xiaoyu, Kang Xinyi, Tang Weichun, Chen Liping
机构信息
Department of Nursing, The Second Affiliated Hospital of Nantong University Nantong 226006, Jiangsu, China.
Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Nantong University Nantong 226006, Jiangsu, China.
出版信息
Am J Transl Res. 2022 Sep 15;14(9):6137-6149. eCollection 2022.
PURPOSE
Pregnancy-induced hypertension (PIH) is a major cause of mortality among pregnant women, fetuses, and newborns. This study assessed the role of long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in PIH development.
METHODS
Serum samples were collected from 30 pregnant women with PIH and 30 healthy pregnant women. Serum UCA1, miR-197-3p, and histone deacetylase-2 (HDAC2) mRNA level was evaluated using quantitative polymerase chain reaction. The expression of UCA1, miR-197-3p and HDAC2 in human placental vascular endothelial cells (HPVECs) was regulated by transfection. HPVECs were treated with hypoxia reoxygenation (H/R) to establish the PIH cell model. Methyl thiazolyl tetrazolium (MTT) assay, the terminal transferase uridyl nick end labelling (Tunel) assay and tubule formation assay were performed to assess the viability, apoptosis and angiogenesis of HPVECs. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were performed to identify the binding between two genes. Western blot analysis was used for protein expression detection.
RESULTS
In pregnant women with PIH, serum UCA1 and HDAC2 expression was downregulated and serum miR-197-3p expression was upregulated. H/R induction decreased the viability and angiogenesis of HPVECs, and increased the apoptosis of HPVECs. In H/R-induced HPVECs, UCA1 upregulation increased the viability and angiogenesis, and decreased the apoptosis. Downregulation of UCA1 had a contrasting result. UCA1 competitively binds to miR-197-3p to upregulate the expression of HDAC2. HDAC2 knockdown counteracted the effect of UCA1 upregulation on the viability, apoptosis and angiogenesis of HPVECs.
CONCLUSIONS
LncRNA UCA1 protected HPVECs from hypoxia-induced damage by regulating the miR-197-3p/HDAC2 axis in PIH.
目的
妊娠高血压综合征（PIH）是导致孕妇、胎儿和新生儿死亡的主要原因。本研究评估了长链非编码RNA（lncRNA）尿路上皮癌相关1（UCA1）在PIH发生发展中的作用。
方法
收集30例PIH孕妇和30例健康孕妇的血清样本。采用定量聚合酶链反应评估血清UCA1、miR-197-3p和组蛋白去乙酰化酶2（HDAC2）mRNA水平。通过转染调节人胎盘血管内皮细胞（HPVECs）中UCA1、miR-197-3p和HDAC2的表达。用缺氧复氧（H/R）处理HPVECs以建立PIH细胞模型。进行甲基噻唑基四氮唑（MTT）法、末端脱氧核苷酸转移酶介导的缺口末端标记（Tunel）法和小管形成试验，以评估HPVECs的活力、凋亡和血管生成。进行双荧光素酶报告基因试验、RNA下拉试验和RNA免疫沉淀试验，以鉴定两个基因之间的结合。采用蛋白质印迹分析检测蛋白质表达。
结果
在PIH孕妇中，血清UCA1和HDAC2表达下调，血清miR-197-3p表达上调。H/R诱导降低了HPVECs的活力和血管生成，并增加了HPVECs的凋亡。在H/R诱导的HPVECs中，UCA1上调增加了活力和血管生成，并减少了凋亡。UCA1下调则产生相反的结果。UCA1竞争性结合miR-197-3p以上调HDAC2的表达。HDAC2敲低抵消了UCA1上调对HPVECs活力、凋亡和血管生成的影响。
结论
lncRNA UCA1通过调节PIH中的miR-197-3p/HDAC2轴保护HPVECs免受缺氧诱导的损伤。
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