Department of Obstetrics, Yantai Yantaishan Hospital, YanTai, Shandong, 264000, China.
Department of Obstetrics, Yantai Yantaishan Hospital, YanTai, Shandong, 264000, China.
Placenta. 2020 Apr;93:34-42. doi: 10.1016/j.placenta.2020.02.001. Epub 2020 Feb 4.
Long noncoding RNA DLX6 antisense RNA 1 (DLX6-AS1) has been reported to be involved in various human diseases, however, its potential role in the pathogenesis of preeclampsia (PE) has not been fully explored.
The levels of DLX6-AS1, microRNA-149-5p (miR-149-5p) and endoplasmic reticulum protein 44 (ERP44) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Some clinicopathological parameters of PE were statistically analyzed. The cell proliferation, invasion and angiogenesis were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT), transwell and tube formation assays, respectively. Levels of all protein were detected by western blot. The target relationship was predicted by StarBase v2.0 and confirmed by dual-luciferase reporter assay.
Higher levels of DLX6-AS1 and ERP44, lower level of miR-149-5p were observed in PE placenta tissues. Compared with PE group with low DLX6-AS1 expression, the systolic blood pressure, diastolic blood pressure and proteinuria levels in the group with high DLX6-AS1 expression were higher, and the infant body weight level was lower. The role of miR-149-5p on these clinicopathological parameters of PE patients was opposite to that of DLX6-AS1, while ERP44 had the same effect as DLX6-AS1. Besides, DLX6-AS1 directly targeted miR-149-5p and miR-149-5p targeted ERP44. The inhibitory impact of DLX6-AS1 overexpression or ERP44 overexpression on proliferation and invasion of trophoblast cells as well as angiogenesis of HUVEC cells was reversed by up-regulating miR-149-5p. We also found that DLX6-AS1 could enhance ERP44 expression by sponging miR-149-5p.
DLX6-AS1 inhibited proliferation and invasion of trophoblast cells, and suppressed angiogenesis of HUVEC cells by miR-149-5p/ERP44 pathway.
长链非编码 RNA DLX6 反义 RNA 1（DLX6-AS1）已被报道参与多种人类疾病，但它在子痫前期（PE）发病机制中的潜在作用尚未得到充分探索。
采用实时定量聚合酶链反应（qRT-PCR）测定 DLX6-AS1、微小 RNA-149-5p（miR-149-5p）和内质网蛋白 44（ERP44）的水平。对 PE 的一些临床病理参数进行统计学分析。通过噻唑蓝（MTT）、transwell 和管形成测定分别评估细胞增殖、侵袭和血管生成。通过 Western blot 检测所有蛋白质的水平。通过 StarBase v2.0 预测靶标关系，并通过双荧光素酶报告基因检测进行验证。
PE 胎盘组织中观察到 DLX6-AS1 和 ERP44 水平升高，miR-149-5p 水平降低。与 DLX6-AS1 低表达的 PE 组相比，DLX6-AS1 高表达组的收缩压、舒张压和蛋白尿水平较高，婴儿体重水平较低。miR-149-5p 对 PE 患者这些临床病理参数的作用与 DLX6-AS1 相反，而 ERP44 的作用与 DLX6-AS1 相同。此外，DLX6-AS1 直接靶向 miR-149-5p，miR-149-5p 靶向 ERP44。上调 miR-149-5p 可逆转 DLX6-AS1 过表达或 ERP44 过表达对滋养细胞增殖和侵袭以及 HUVEC 细胞血管生成的抑制作用。我们还发现，DLX6-AS1 可以通过海绵 miR-149-5p 来增强 ERP44 的表达。
DLX6-AS1 通过 miR-149-5p/ERP44 通路抑制滋养细胞增殖和侵袭，并抑制 HUVEC 细胞血管生成。
