LncRNA FAM99A is downregulated in preeclampsia and exerts a regulatory effect on trophoblast cell invasion, migration and apoptosis

Abstract

Preeclampsia (PE) is a complication of pregnancy, and a leading cause of maternal mortality and morbidity worldwide. Recently, the dysregulation of long non-coding RNAs (lncRNAs) has been reported to contribute to the pathogenesis and progression of PE. This study aimed to examine the alterations in the lncRNA family with sequence similarity 99 member A (FAM99A) in PE and its effects on trophoblasts. The results of reverse transcription-quantitative PCR indicated that the expression levels of FAM99A were downregulated in placental tissues from women with severe PE compared with in those from controls. A Transwell invasion assay and wound healing assay revealed that overexpression of FAM99A promoted invasion and migration of HTR-8/SVneo cells; conversely, knockdown of FAM99A suppressed the invasive and migratory abilities of HTR-8/SVneo cells. Flow cytometry demonstrated that FAM99A overexpression induced a decrease in the apoptotic rate of cells, whereas knockdown of FAM99A increased the apoptotic rate of HTR-8/SVneo cells. Western blot analysis revealed that overexpression of FAM99A decreased the protein expression levels of cleaved caspase-3, cleaved caspase-9 and Bax, and increased Bcl-2 protein expression, whereas knockdown of FAM99A had the opposite effects on these protein levels. Overexpression of FAM99A also decreased caspase-3 activity in HTR-8/SVneo cells; however, knockdown of FAM99A increased caspase-3 activity. In addition, overexpression of FAM99A enhanced Wnt/β-catenin signaling activity, whereas FAM99A knockdown exerted an inhibitory effect on the Wnt/β-catenin signaling activity in HTR-8/SVneo cells. In conclusion, these results indicated that FAM99A may serve a role in modulating the functions of trophoblasts, partially via targeting Wnt/β-catenin signaling.