Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial–mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia

Abstract

BackgroundMounting evidence has revealed that abnormal expression of circular RNAs play pivotal roles in many human diseases including preeclampsia (PE). While human sapiens circular RNA 0007121 (hsa_circ_0007121) has been verified to be downregulated in human placental tissues, the underlying mechanisms were still unclear. This research aims to investigate the effect and underlying mechanisms of hsa_circ_0007121 in preeclampsia.MethodsThe expression of hsa_circ_0007121, microRNA (miR)-182-5p, and placental growth factor (PGF) was assessed by quantitative reverse transcription polymerase chain reaction in PE placentas relative to the expression in normal pregnancy placentas. After transfection, cell counting kit-8 assay was employed to detect cell proliferation. Cell migration and invasion were tested by the transwell assay. The relative level of epithelial–mesenchymal transition (EMT)-related proteins in HTR-8/SVneo cells and PGF in placentas samples were measured by western blot. The relationship between miR-182-5p and hsa_circ_0007121 or PGF was predicated by circular RNA interactome or ENCORI and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay.ResultsThe levels of hsa_circ_0007121 and PGF were significantly declined in PE placental tissues and HTR-8/SVneo cells, whereas miR-182-5p had an opposite result. Downregulation of hsa_circ_0007121 obviously inhibited HTR-8/SVneo cell proliferation, migration, invasion, and EMT, while upregulation of hsa_circ_0007121 promoted this process. Besides, miR-182-5p was a target gene of hsa_circ_0007121 and could target PGF. Further analysis indicated that hsa_circ_0007121 regulated the proliferation, migration, invasion, and EMT of HTR-8/SVneo cells via altering PGF expression by interacting with miR-182-5p.ConclusionHsa_circ_0007121 mediated the progression of PE via miR-182-5p/PGF axis.

Circ_0037078 promotes trophoblast cell proliferation, migration, invasion and angiogenesis by miR‐576‐5p/IL1RAP axis

“…13,21 For instance, hsa_circ_0007121 contributed to the proliferation, migration, invasion, and EMT of trophoblast cells by sequestering miR-182-5p. 22 Besides that, circCRAMP1L was an independent predictor of PE, and restoration of circCRAMP1L in trophoblast cells promote cell proliferation and invasion. 23 In the present study, we also observed an increased expression of circ_0037078 in the placental tissues of PE, knockdown of circ_0037078 enhanced the invasion, migration and proliferation of HTR8/SVneo cells, which was consistent with previous study.…”

Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

“…It is usually diagnosed after week 20 of gestation and is characterized by maternal hypertension and proteinuria [ 14 ]. An increasing number of studies have been investigating PE etiopathogenesis, showing that ncRNAs, especially miRNAs [ 14 ], circRNAs [ 94 , 95 , 96 ], and lncRNAs [ 44 ] detectable in both maternal placenta and plasma, have a crucial role in endothelial angiogenic function and placentation [ 97 , 98 , 99 ].…”

Identification and comparison of circular RNAs in preeclampsia

“…Most of these circRNAs were identified from the trophoblast cell or human placenta using human circRNA microarray or using publicly available datasets from the Gene Expression Omnibus (GEO) databaseand meta-analyzing them with bioinformatics techniques (Zhou et al, 2018;. In addition, Hsa_circ_0007121 was reported to mediate the progression of PE via miR-182-5p/placental growth factor (PGF) axis (Gai et al, 2020). CircLRRK1 was identified to suppress the proliferation, migration and invasion of trophoblast cells via miR-223-3p/PI3K/AKT axis (Tang, Zhang & Han, 2020).…”