Retracted: HDAC2‐mediated proliferation of trophoblast cells requires the miR‐183/FOXA1/IL‐8 signaling pathway

Abstract

Pre‐eclampsia (PE) is a major cause of maternal and perinatal death. Previous research has indicated the role of histone deacetylase 2 (HDAC2) in the pathogenesis of PE but the relevant molecular mechanisms are unknown. However, there is hitherto little information concerning the molecular mechanism behind HDAC2 in PE. Herein, we hypothesized that HDAC2 promotes trophoblast cell proliferation and this requires the involvement of microRNA‐183 (miR‐183), forkhead box protein A1 (FOXA1), and interleukin 8 (IL‐8). We collected placental specimens from 30 PE affected and 30 normal pregnant women. HDAC2 and FOXA1 were poorly expressed while miR‐183 and IL‐8 were highly expressed in placental tissues in PE. In vitro, HDAC2 overexpression enhanced the proliferation, migration, and invasion of human trophoblast cells HTR‐8/SVNEO. HDAC2 inhibited the expression of miR‐183 by diminishing H4 acetylation in the miR‐183 promoter region. miR‐183 inhibition by its specific inhibitor increased the expression of FOXA1 and thus enhanced HTR‐8/SVNEO cell proliferation, migration, and invasion. FOXA1, a transcriptional factor, enhanced HTR‐8/SVNEO cell proliferation, migration, and invasion by inhibiting the transcription of IL‐8. We also observed HDAC2 knockdown was lost upon FOXA1 overexpression, suggesting that HDAC2 could promote HTR‐8/SVNEO proliferation, migration, and invasion through the miR‐183/FOXA1/IL‐8 pathway. In summary, the results highlighted the role of the HDAC2/miR‐183/FOXA1/IL‐8 pathway in PE pathogenesis and thus suggest a novel molecular target for PE.

Histone deacetylase HDAC2 silencing prevents endometriosis by activating the HNF4A/ARID1A axis

“…In addition, another research unveiled that HDAC2‐targeting shRNA caused suppression of the in vitro migration and invasion ability of colorectal cancer cells, which was concordant with our finding 16 . Also, ectopic expression of HDAC2 could lead to facilitation of the proliferation, migration and invasion of human trophoblast cells HTR‐8/SVNEO 17 …”

SMAD4 Inhibits Granulosa Cell Apoptosis via the miR-183-96-182 Cluster and FoxO1 Axis

“…The miR-183-96-182 cluster is well known to be a typical miRNA cluster because its three components have similar seed sequences and common target genes, and even play similar biological functions [10,14]. In the present study, we demonstrated that the miR-183-96-182 cluster members may share a common promoter, which is activated by the same Increasing evidence suggests that the miR-183-96-182 cluster has a common putative promoter in humans [4,30,35,36]. The miR-183-96-182 cluster members were coupregulated or co-downregulated in β -Cateninoverexpressing or β-Catenin-silencing cells; mechanically, β-Catenin directly binds to the putative promoter located in −8000 nt ~−6000 nt of 5 regulatory region of the miR-183-96-182 cluster and thereby activates the transcription of this cluster in AGS cells [30] and hepatocellular carcinoma cells [31].…”

“…The miR-183-96-182 cluster members were coupregulated or co-downregulated in β -Cateninoverexpressing or β-Catenin-silencing cells; mechanically, β-Catenin directly binds to the putative promoter located in −8000 nt ~−6000 nt of 5 regulatory region of the miR-183-96-182 cluster and thereby activates the transcription of this cluster in AGS cells [30] and hepatocellular carcinoma cells [31]. Furthermore, some transcription factors such as STAT5 [37], MYCN [38], ZEB1 [39], and KLF4 [40], and several epigenetic modulators such as HDAC2 [36,38] have been shown to interact with the putative promoter of the miR-183-96-182 cluster to positively or negatively regulate its transcription and function. Here, we further showed that the miR-183-96-182 cluster members may share a common promoter and a common transcription activator SMAD4 in pigs.…”

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

“…First, it has been validated that TF FOXA1 can induce the expression of target genes CD274 and IL8 by directly binding to their promoter region [ 124 , 125 ]. It is worth noting that the MIR183/FOXA1/CXCL8 pathway activated by HDAC2 has been investigated in a previous study [ 126 ]. In Figure 4 , we show that this pathway is, instead, mediated by TF ZEB1 and incorporated with the downstream of the TGFβ signaling pathway.…”