Department of Obstetrics, Shanxi Provincial People's Hospital, Taiyuan City, Shanxi Province, China.
Hypertens Res. 2022 Aug;45(8):1334-1344. doi: 10.1038/s41440-022-00934-z. Epub 2022 Jun 13.
Emerging evidence has shown that circular RNAs (circRNAs) play vital roles in the progression of diverse human diseases. However, the functions of circRNAs in preeclampsia (PE) are largely unknown. In this study, we aimed to explore the functions of the circRNA furin, paired basic amino acid cleaving enzyme (circ_FURIN) in PE development. qRT-PCR and western blot analyses were conducted to determine the levels of circ_FURIN, miR-34a-5p and transcription factor AP-2 alpha (TFAP2A). A Cell Counting Kit-8 (CCK-8) assay and a 5'-ethynyl-2'-deoxyuridine (EdU) incorporation assay were utilized to evaluate the cell proliferation ability. Transwell assays were adopted to estimate cell migration and invasion. A dual-luciferase reporter assay and an RNA pulldown assay were utilized to analyze the relationships among circ_FURIN, miR-34a-5p and TFAP2A. It was found that circ_FURIN was downregulated in PE placental tissues and hypoxia-treated placental trophoblast cells. Overexpression of circ_FURIN promoted trophoblast cell proliferation, migration and invasion under hypoxic conditions. Circ_FURIN functioned as the sponge for miR-34a-5p. MiR-34a-5p overexpression abrogated the effects of circ_FURIN on the proliferation, migration and invasion of trophoblast cells under hypoxic conditions. In addition, TFAP2A was demonstrated to be the target gene of miR-34a-5p. TFAP2A silencing ameliorated the promotive effects of miR-34a-5p inhibition on trophoblast cell proliferation, migration and invasion under hypoxic conditions. In conclusion, circ_FURIN enhanced trophoblast cell proliferation, migration and invasion under hypoxic conditions by elevating TFAP2A expression through sponging miR-34a-5p.
新兴证据表明，环状 RNA（circRNAs）在多种人类疾病的进展中发挥着重要作用。然而，circRNAs 在子痫前期（PE）中的功能在很大程度上仍是未知的。在本研究中，我们旨在探索 furin 环状 RNA（circ_FURIN）在 PE 发展中的功能。qRT-PCR 和 Western blot 分析用于确定 circ_FURIN、miR-34a-5p 和转录因子 AP-2 alpha（TFAP2A）的水平。细胞计数试剂盒-8（CCK-8）测定和 5'-乙炔基-2'-脱氧尿苷（EdU）掺入测定用于评估细胞增殖能力。Transwell 测定用于估计细胞迁移和侵袭。双荧光素酶报告基因测定和 RNA 下拉测定用于分析 circ_FURIN、miR-34a-5p 和 TFAP2A 之间的关系。结果发现，circ_FURIN 在 PE 胎盘组织和缺氧处理的胎盘滋养层细胞中下调。circ_FURIN 的过表达促进了缺氧条件下滋养层细胞的增殖、迁移和侵袭。circ_FURIN 作为 miR-34a-5p 的海绵发挥作用。miR-34a-5p 的过表达消除了 circ_FURIN 对缺氧条件下滋养层细胞增殖、迁移和侵袭的影响。此外，TFAP2A 被证明是 miR-34a-5p 的靶基因。miR-34a-5p 抑制减轻了 TFAP2A 抑制对缺氧条件下滋养层细胞增殖、迁移和侵袭的促进作用。总之，circ_FURIN 通过海绵吸附 miR-34a-5p 来提高 TFAP2A 的表达，从而增强缺氧条件下滋养层细胞的增殖、迁移和侵袭。
