RETRACTED: The YY1-HOTAIR-MMP2 Signaling Axis Controls Trophoblast Invasion at the Maternal-Fetal Interface

Abstract

We aimed to determine the effect of YY1 expression on the expression profile of long noncoding RNAs (lncRNAs) in trophoblasts, and we studied the involvement of certain lncRNAs and YY1 in the pathogenesis of recurrent miscarriage (RM). RT2 lncRNA PCR arrays revealed that YY1 overexpression in trophoblasts significantly promoted the expression of the HOX transcript antisense RNA HOTAIR and demonstrated that HOTAIR expression was significantly lower in the RM trophoblasts than in control trophoblasts. Ectopic HOTAIR overexpression and knockdown experiments revealed that it was a novel target of YY1. Bioinformatics analysis identified two YY1-binding sites in the HOTAIR promoter region, and chromatin immunoprecipitation (ChIP) analysis verified that YY1 binds directly to its promoter region. Interestingly, HOTAIR overexpression enhanced trophoblast invasion in an ex vivo explant culture model, while its knockdown repressed these effects. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) label-free quantitative proteomics screening revealed that HOTAIR overexpression activated phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling in trophoblasts. In an ex vivo explant culture model, HOTAIR overexpression effectively elevated matrix metalloproteinase 2 (MMP2) expression via the PI3K-AKT signaling pathway, enhancing trophoblast migration and invasion. These findings reveal a new regulatory pathway in which YY1 activates PI3K-AKT signaling via HOTAIR, promoting MMP2 expression, suggesting that HOTAIR is a potential therapeutic target for RM.

RETRACTED: Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR

“…We also found that HOTAIR regulates trophoblast migration and invasion, thereby contributing to the pathology of RM and/or pre-eclampsia, suggesting HOTAIR to be a potential therapeutic target for RM. 15 This indicates that HOTAIR acts as an important non-coding RNA (ncRNA); however, the regulatory mechanisms controlling HOTAIR stability are largely unknown.…”

SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN‐γ‐induced STAT1 expression and activation in recurrent miscarriage

“…One potential concern is that GDC-0941 is known as a potent inhibitor of PI3K/AKT pathway, which inhibits both PI3K and AKT phosphorylations as well as the downstream targets of AKT signaling, 45,46 and some researchers also use GDC-0941 as a p-AKT inhibitor. 47 However, there is a defect in this study that we did not use specific p-AKT inhibitors such as AZD5363 or GDC-0068 to elaborate our findings mechanistically more in depth.…”

Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

“…The number of migrated cells decreased in the BPDE-treated group in a dose-dependent manner ( Figure 4(c) ). Previous studies have suggested that the PI3K/AKT/MMP2 signaling pathway was involved in trophoblast migration [ 19 ]. To determine whether BPDE inhibits trophoblast cell migration through this pathway, the mRNA levels of PI3K, AKT, and MMP2 were analyzed by qRT-PCR assays.…”