Novel piRNA Regulates PIWIL1 to Modulate the Behavior of Placental Trophoblast Cells and Participates in Preeclampsia.

Objectives: This study is aimed at investigating the role of PIWIL1/piRNA in the development of preeclampsia. Methods: High-throughput sequencing was performed in 5 preeclampsia and 5 normal placentas to get a piRNA expression profile. WGCNA network was constructed to find hub piRNAs. Through target gene prediction and protein interaction network analysis, we found the potential relationship between the key genes and PIWIL1. Subsequently, we detected the expression of PIWIL1 in 35 preeclampsia and 29 normal placental tissues. Overexpression and inhibition of PIWIL1 in HTR-8/SVneo trophoblast cells were achieved by transfecting an overexpression vector and siRNAs, respectively. Cell proliferation, apoptosis, and invasion were assessed using CCK-8, flow cytometric, and transwell assays, respectively. Results: It was found that a total of three piRNAs were upregulated in preeclampsia (pir-hsa-1256314, uniq_271431, and uniq_277797). And two target genes with the highest connectivity (FXR1 and DDX6) both pointed to PIWIL1. PIWIL1 expression was significantly lower in preeclampsia. In vitro studies linked PIWIL1 expression to trophoblast overgrowth. Overexpression of PIWIL1 remarkably promoted cell proliferation and invasion and inhibited apoptosis of HTR-8/SVneo cells and vice versa. Conclusions: PIWIL1/piRNA may be involved in the pathogenesis of preeclampsia by inhibiting the proliferation and invasion and promoting the apoptosis of placental trophoblasts. This study was registered with the China Clinical Trials Registry (http://www.clinicaltrials.gov): registration number ChiCTR1900027479.