Silencing of AFAP1‐AS1 lncRNA impairs cell proliferation and migration by epigenetically promoting DUSP5 expression in pre‐eclampsia

Abstract

As a unique and common obstetric complication of pregnant women, pre‐eclampsia (PE) has been the first leading cause of maternal and perinatal morbidity and mortality in the world. Mounting studies have demonstrated that an abnormality of long noncoding RNA (lncRNA) expression was related to the pathological process of PE. Here, we showed that lncRNA AFAP1‐AS1 was markedly downregulated in pre‐eclamptic placentas. We further investigated the mechanism underlying the regulatory role of AFAP1‐AS1 in PE using human trophoblast cells. In vitro functional assays revealed that AFAP1‐AS1 knockdown inhibited trophoblast proliferation, migration, and invasion. Moreover, AFAP1‐AS1 interacts with EZH2 and inhibits DUSP5 expression through modulating H3K27m3 in the DUSP5 promoter of trophoblast cells, thus being involved in PE pathogenesis. Overall, these findings suggest that AFAP1‐AS1 could potentially become a prognostic biomarker as well as a new therapeutic target for PE.

Human Papillomavirus Type 16 Early Protein E7 Activates Autophagy through Inhibition of Dual-Specificity Phosphatase 5

“…Our current study showed that expression of DUSP5 is severely repressed in cervical cancer tissues. Consistent with our results, DUSP5 expression in pre-eclampsia inhibits trophoblast proliferation, migration and invasion [ 47 ]. In addition, it has been shown that DUSP5-mediated ERK suppression can serve as a protective mechanism by blocking pulmonary vascular smooth muscle cell proliferation, by preventing pulmonary hypertension and right ventricular cardiac hypertrophy [ 48 ] and by inhibiting inflammation in adipocytes [ 35 ].…”

SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/PCDH11X axis and activates PI3K/Akt signaling pathway

“…In addition, lncRNA AFAP1-AS1 silencing epigenetically caused the upregulation of DUSP5, thereby restricting trophoblast proliferation and migration in PE. 28 Similarly, in the present study, it was found that SNHG22 was downregulated in PE placentas, and overexpression of SNHG22 promoted migration and invasion of HTR-8/Svneo and JEG-3 cells, while they were inhibited by SNHG22 silencing, which confirmed the contribution of SNHG22 to biological behaviors of trophoblasts.…”

A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia

“…All placental tissues were washed with sterile saline and stored in liquid nitrogen. The clinicopathological characteristics of healthy pregnant women and PE patients are summarized in Table S1 (published by Zhang et al 54 ). The study protocol was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University.…”