A novel regulated network mediated by downregulation HIF1A-AS2 lncRNA impairs placental angiogenesis by promoting ANGPTL4 expression in preeclampsia

Abstract

Preeclampsia (PE) is the predominant medical condition leading to maternal and fetal mortality, and the lack of effective treatment increases its risk to the public health. Among the numerous predisposing factors, the ineffectual remodeling of the uterine spiral arteries, which can induce abnormal placental angiogenesis, has been focused to solve the pathogenesis of PE. According to the preceding research results, abnormal expression of long non-coding RNAs (lncRNA)s could be associated with the pathological changes inducing PE. To be more specific, lncRNA HIF1A-AS2 was proposed for its potential to participate in the molecular mechanisms underlying PE. In vitro, in trophoblast cell lines HTR-8/SVneo and human umbilical vein endothelial cells HUVECs, HIF1A-AS2 knockdown inhibited cell proliferation, migration and tube formation. Mechanistically, transcription factor FOXP1 could regulate the expression of HIF1A-AS2. Moreover, a series of assays, including RNA pull down and mass spectrometry, RNA immunoprecipitation and chromatin immunoprecipitation assay, revealed that HIF1A-AS2 interacted with Lamin A/C (LMNA) to inhibit ANGPTL4 expression in trophoblast cells, thus further participating in the progression of PE. Taken together, these findings suggested that further analysis on HIF1A-AS2 could contribute to the development of prospective therapeutic strategy for PE.

Aspirin in Invasive Function of Hypoxic HTR-8/SVneo by Modulating the Urothelial Carcinoma-Associated 1/ microRNA-18a/HIF-1α Pathway

“…A study has shown that HIF-1 is a crucial link in the pathogenesis of PE [43] . As a component of HIF-1, HIF-1α regulates multiple pathways mediating abnormal PE placental vascular remodeling [44,45] . Primarily, HIF-1α can activate anti-angiogenic and inhibit pro-angiogenic factors, such as soluble FMS-Like Tyrosine kinase-1 (FLT1), VEGFA, Notch homolog 1 [46] .…”

The relationship between preeclampsia risk and SENCR rs555172 gene polymorphism and expression

“…LncRNAs gene expression alteration could influence the trophoblast cell. Normal endothelial function is required for successful placental implantation, maternal and fetal circulation networks [16] and also Line proliferation, migration, and invasion [17][18][19]. Dong et al reported a correlation among lncRNA MIR193BHG with systolic and diastolic blood pressure and urine protein [20].…”

IGF2BP2 enhances LincRNA01116 stability via m6A: A potential biomarker and therapeutic target for patients with pre‐eclampsia

“…The protocol for animal experiments was approved by the Animal ethics committee of Nanjing Medical University (IACUC‐2202026). The plug assay was performed as previously described 19 . The tumors were extracted, photographed, and analyzed using IHC (anti‐CD31 antibody).…”

“…The plug assay was performed as previously described. 19 The tumors were extracted, photographed, and analyzed using IHC (anti-CD31 antibody).…”