Preeclampsia-associated lncRNA FEZF1-AS1 regulates cell proliferation and apoptosis in placental trophoblast cells through the ELAVL1/NOC2L axis

Abstract

Background LncRNAs have been shown to be involved in and control the biological processes of multiple diseases, including preeclampsia (PE). The impairment of trophoblast cell proliferation is recognized as a significant anomaly contributing to the development of PE. LncRNA FEZF1-AS1 was found downregulated in placental tissues of PE patients. However, the precise regulatory mechanism of FEZF1-AS1 in placental trophoblast proliferation and apoptosis remains unclear. Results In this study, we conducted an investigation into the expression levels of FEZF1-AS1 and NOC2L in placental tissues obtained from patients diagnosed with PE. Subsequently, we employed CCK-8 and EdU assays to quantify cell proliferation, while TUNEL staining and western blot for apoptosis-related protein detection to assess apoptosis. Furthermore, the interactions between FEZF1-AS1 and ELAVL1, as well as NOC2L and ELAVL1, were confirmed through the implementation of RIP and RNA pull-down assays. We found a downregulation of lncRNA FEZF1-AS1 and NOC2L in placental tissues of PE patients. Overexpression of FEZF1-AS1 or NOC2L resulted in increased cell proliferation and inhibition of apoptosis, whereas knockdown of FEZF1-AS1 or NOC2L had the opposite effect. In addition, lncRNA FEZF1-AS1 stabilized NOC2L mRNA expression by interacting with ELAVL1. Moreover, partial reversal of the effects of FEZF1-AS1 overexpression on cell proliferation and apoptosis was observed upon suppression of ELAVL1 or NOC2L. Conclusions PE related lncRNA FEZF1-AS1 could regulate apoptosis and proliferation of placental trophoblast cells through the ELAVL1/NOC2L axis.

Potential molecular mechanisms and clinical implications of piRNAs in preeclampsia: a review

“…miR-145-5p mediates trophoblast cell invasion in female patients with EOPE by regulating TNF expression [ 55 ].Zhang et al found that lncRNA DANCR activates the PI3K/AKT pathway through downregulation of miR-214-5p expression, promoting chorionic trophoblast cell migration and invasion of chorionic trophoblasts [ 56 ]. Zhao et al found that lncRNA FEZF1-AS1 regulates apoptosis and proliferation of placental trophoblasts by stabilizing NOC1L mRNA expression through interaction with ELAVL2 [ 57 ]. In addition, miR-574-5p and miR-1972 may act as anti-angiogenic factors that inhibit endothelial cell proliferation and migration and reduce the ability of endothelial cells to form angioid structures by downregulating the expression of the cell proliferation marker MKI67 [ 58 ].…”