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.
Highlights
Preeclampsia (PE) affected 2–8% of pregnancies worldwide and led to 46,900 deaths in 2015 [1]
HTR-8/SVneo cell line is human being chorial trophocyte cell that was always used for the study of trophoblast biology and placental function, which may improve our understanding of diseases related to tumor progression, abnormal placentation hypoinvasiveness in preeclampsia, and hyperinvasiveness in trophoblastic neoplasms [8,9]
The effect of hsa_circ_0007121 on PE was further investigated, and we detected its level in HTR-8/SVneo cells after transfection with circ-NC, hsa_circ_0007121, si-NC, or si-hsa_circ_0007121
Summary
Preeclampsia (PE) affected 2–8% of pregnancies worldwide and led to 46,900 deaths in 2015 [1]. Hypertension, diabetes mellitus, proteinuria, obesity, family history, multiple pregnancies, and thrombotic vascular disease are the risk factors for PE [2]. Growing evidence indicated that epithelial–mesenchymal transition (EMT) was related to the development of PE [6,7]. HTR-8/SVneo cell line is human being chorial trophocyte cell that was always used for the study of trophoblast biology and placental function, which may improve our understanding of diseases related to tumor progression, abnormal placentation hypoinvasiveness in preeclampsia, and hyperinvasiveness in trophoblastic neoplasms [8,9]. The potential pathogenesis of PE is barely elucidated, we chose HTR-8/Svneo cell as a study subject in vitro
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