Anqing Municipal Hospital, Anhui Medical University, Anqing, 246000, China.
Department Gynecology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230032, China.
Biochem Biophys Res Commun. 2020 Oct 22;531(4):472-479. doi: 10.1016/j.bbrc.2020.06.117. Epub 2020 Aug 15.
Recurrent spontaneous abortion (RSA), defined as two or more consecutive pregnancy losses before 12 weeks of gestation with or without previous live births. Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that play important roles in gene expression regulation and trophoblasts function during embryo development. This study aimed to evaluate the function mechanism of circRNAs regulating trophoblasts function in the occurrence and progression RSA. Through overexpression and down-regulation of circ-ZUFSP, we investigated the effect of circ-ZUFSP on the function of trophoblasts and found loss of circ-ZUFSP suppressed trophoblasts migration and invasion in vitro. Moreover, loss of circ-ZUFSP regulated trophoblasts migration and invasion via regulation of miR-203. Furthermore, STOX1 was revealed to a target of miR-203, and down-regulation of STOX1 reversed circ-ZUFSP enhanced cell invasion, suggesting that circ-ZUFSP might regulate STOX1 expression through sponging miR-203 in HTR-8/SVneo cells. In addition, low expression of circ-ZUFSP, STOX1 and high expression of miR-203 were testified in placental tissues of RSA mice. Our study demonstrated a molecular mechanism of circ-ZUFSP regulating trophoblasts migration and invasion, which might provide a novel indicator for early diagnosis and potential treatment of RSA.
复发性自然流产(RSA)定义为两次或两次以上妊娠 12 周前连续流产,无论是否有以前的活产。环状 RNA(circRNA)是一类新的内源性非编码 RNA,在胚胎发育过程中基因表达调控和滋养细胞功能中发挥重要作用。本研究旨在评估 circRNA 调节滋养细胞功能在 RSA 发生和进展中的作用机制。通过 circ-ZUFSP 的过表达和下调,我们研究了 circ-ZUFSP 对滋养细胞功能的影响,发现 circ-ZUFSP 的缺失抑制了滋养细胞的迁移和侵袭。此外,circ-ZUFSP 通过调节 miR-203 来调节滋养细胞的迁移和侵袭。进一步揭示 STOX1 是 miR-203 的靶基因,下调 STOX1 逆转了 circ-ZUFSP 增强的细胞侵袭,表明 circ-ZUFSP 可能通过在 HTR-8/SVneo 细胞中海绵 miR-203 来调节 STOX1 表达。此外,在 RSA 小鼠的胎盘组织中证实了 circ-ZUFSP、STOX1 表达降低和 miR-203 表达升高。本研究阐明了 circ-ZUFSP 调节滋养细胞迁移和侵袭的分子机制,为 RSA 的早期诊断和潜在治疗提供了新的指标。