International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
Am J Reprod Immunol. 2019 Jan;81(1):e13048. doi: 10.1111/aji.13048. Epub 2018 Sep 17.
Human pregnancy is a complex biological process, and spontaneous abortion is the most common complication of pregnancy. LncRNAs have been identified that play key roles in a variety of human diseases. Recently, lncRNAPVT1 was reported to relate to the pathogenesis and progression of pregnancy. However, the role and underlying mechanism of PVT1 in trophoblast cell dysfunction in spontaneous abortion remain largely unknown.
The effects of PVT1, miR-424, and eIF5A on HTR8 cells and human villi tissues from spontaneous or induced abortions were investigated using CCK-8 assay, EdU assay, real-time polymerase chain reaction, Western blotting, cell transfection assays, cell migration assays, and luciferase reporter gene assays.
Overexpression of PVT1 promoted HTR8 cell viability, proliferation, and migration. Suppression of PVT1 promoted miR-424 expression, and miR-424 could modulate the effects of PVT1 in HTR8 cells. MiR-424 exerted its function via regulation of eIF5A expression in HTR8 cells. PVT1 and eIF5A expression were decreased and miR-424 was increased in clinical samples from spontaneous abortion, compared to samples from elective induced abortion.
PVT1 regulates trophoblast cell function via modulation of a PVT1/miR-424/eIF5A pathway.
人类妊娠是一个复杂的生物学过程,自然流产是妊娠最常见的并发症。已经发现了一些 lncRNAs,它们在多种人类疾病中发挥关键作用。最近,lncRNAPVT1 被报道与妊娠的发病机制和进展有关。然而,PVT1 在自然流产中滋养细胞功能障碍中的作用及其潜在机制在很大程度上仍不清楚。
使用 CCK-8 测定法、EdU 测定法、实时聚合酶链反应、Western blot 印迹、细胞转染实验、细胞迁移实验和荧光素酶报告基因实验研究 PVT1、miR-424 和 eIF5A 对 HTR8 细胞和来自自然或人工流产的人绒毛组织的影响。
过表达 PVT1 促进 HTR8 细胞活力、增殖和迁移。抑制 PVT1 促进 miR-424 的表达,miR-424 可以调节 HTR8 细胞中 PVT1 的作用。miR-424 通过调节 HTR8 细胞中 eIF5A 的表达发挥其功能。与人工诱导流产的样本相比,自然流产的临床样本中 PVT1 和 eIF5A 的表达降低,而 miR-424 的表达升高。
PVT1 通过调节 PVT1/miR-424/eIF5A 通路来调节滋养细胞功能。