Abstract
Background: Mounting evidence has revealed that impaired spiral artery remodeling, placental dysfunction, and inadequate trophoblast invasion are closely correlated with the etiology and pathogenesis of pre-eclampsia (PE). However, the detailed molecular pathology of PE remains unclear. Although circRNAs, as a new type of stable and abundant endogenous noncoding RNA, have been proven to be essential to the pathogenesis of various diseases, their role in PE requires further verification. In this context, it is necessary to unveil the roles of circRNAs in regulating the migration and invasion of extravillous trophoblasts. Methods: To exploit the roles of circRNAs together with PAPPA2 in the pathogenesis of PE, circPAPPA2 (hsa_circ_0111277) was applied in this study to determine the molecular mechanisms controlling trophoblastic invasion and migration in PE. Findings: In this study, using quantitative real-time PCR, we confirmed that circPAPPA2 was upregulated in PE placentas relative to the level in normal pregnancy placentas. In addition, positive correlations between hsa_circ_0111277 expression and PE-related factors (proteinuria level at 24 h and placental weight) were identified by Pearson’s analysis based on the clinical data of 25 PE patients. Moreover, fluorescence in situ hybridization analysis illustrated that circ_0111277 was preferentially localized within the cytoplasm. Mechanistically, circ_0111277 sponged hsa-miR-494-3p in trophoblast cells to attenuate the latter’s repression by regulating HTRA1/Notch-1 expression. Interpretation: In conclusion, trophoblast cell migration and invasion were shown to be promoted and modulated by the circPAPPA2/miR-494-3p/HTRA1/Notch-1 axis, which provides useful insight for exploring a new therapeutic approach for PE. Funding Statement: This study was supported by the National Nature Science Foundation of China (No. 81771660, 81741017), Guangdong Natural Science Foundation (2018A030310162, 18zxxt56), and 5010 projects at Sun Yat-Sen University (2012006). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital and the enrolled subjects provided informed consent to participate in this research.
Published Version
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