ANKRD37 inhibits trophoblast migration and invasion by regulating the NF‐κB pathway in preeclampsia

Abstract

Background Inadequate trophoblast invasion is associated with preeclampsia (PE). Ankyrin repeat domain protein 37 (ANKRD37) has been reported to be abnormally expressed in PE placentas. However, the role of ANKRD37 in trophoblasts has not been investigated. We aimed to determine the functions of ANKRD37 in PE and to explore the molecular mechanisms. Methods Here, fluorescence in situ hybridization, immunohistochemistry, Western blotting and quantitative real‐time polymerase chain reaction were used to detect protein and mRNA expression levels. Cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, flow cytometry, wound healing assay, transwell assay and RNA sequencing were performed to investigate the role of ANKRD37 and the underlying mechanism in HTR8/SVneo and JEG‐3 cells, and extravillous explant cultures were used to evaluate the migration and invasion abilities of extravillous cytotrophoblasts. Results We found that ANKRD37 expression was upregulated in PE placentas compared to normal pregnancy placentas. ANKRD37 knockdown enhanced trophoblast migration and invasion, promoted extravillous explant outgrowth, and regulated the expression of key invasion proteins, whereas ANKRD37 overexpression exerted the opposite effects. RNA sequencing indicated that nuclear factor‐kappa B (NF‐κB) was the potential downstream pathway of ANKRD37, which was confirmed by the change in p‐p65 and p‐IκBα expression in JEG‐3 and HTR8/SVneo cells. Conclusions Our findings suggest that high expression of ANKRD37 inhibits trophoblast cell migration and invasion possibly via the NF‐κB pathway, and may be related to the development of PE.

Unveiling immune tolerance pathways in preeclampsia placenta: implications for molecular targets and discovery of potential biomarkers

“…The area under the curve (AUC) values in ROC analysis further support their potential diagnostic efficacy in distinguishing preeclampsia patients from normal controls. Studies have shown that ANKRD37 high expression may inhibit the migration and invasion of trophoblast cells through the NF- κ B pathway, potentially contributing to PE development ( 30 ). In the hypoxic-ischemic environment of preeclampsia, a novel member of the CRH peptide family significantly increases Ucn2 and Ucn3, further promoting the response to oxidative stress in the placenta ( 31 ).…”

Combined analysis of the effects of hypoxia and oxidative stress on DNA methylation and the transcriptome in HTR‐8/SVneo trophoblast cells

“… 45 Increased expression of ANKRD37 has been observed in preeclamptic placentas and may inhibit trophoblast cell migration and invasion through the NF‐κB pathway. 46 Researchers propose that ANKRD37 could serve as a novel marker for PE. 47 PFKFB3 , in contrast, is an enzyme involved in glucose metabolism.…”

Abnormal expression of SLIT3 induces intravillous vascularization dysplasia in ectopic pregnancy

“…The correlation between SLIT3 and villous capillaries will be further confirmed by expanding the sample size in the future, with the aim of providing new biomarkers for predicting abnormalities in villi and villous vascular development. Additionally, although HTR8/SVneo is widely used as a model to study the invasion, migration, metabolism and other functions of placental trophoblast cells ( Basak et al., 2018 ; Tan et al., 2022 ; Yin et al., 2022 ), it cannot fully reflect the real situation of trophoblast cells in vivo due to its own limitations; therefore, primary trophoblast cells should be used to further validated the findings of this study in the future. Furthermore, the specific molecular mechanisms by which miR-491-5p and SLIT3 regulate EP have not been fully investigated.…”