A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia

Xu, Yetao; Wu, Dan; Hui, Bingqing; Shu, Lijun; Tang, Xi; Wang, Cong; Xie, Jiaheng; Yin, Yin; Sagnelli, Matthew; Yang, Nana; Jiang, Ziyan; Zhang, Yuanyuan; Sun, Lichao

doi:10.1016/j.ymthe.2022.01.043

Cited by 25 publications

(19 citation statements)

References 57 publications

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“…The expression of FOXP1 was significantly downregulated in PE placenta compared with that in control. The same trend was also obtained in the animal model of preeclampsia ( Xu et al, 2022 ). Subsequently, FOXP1 expression at both RNA and protein levels in the HTR-8/SVneo were silenced with siRNAs ( Figures 4A,B ), and in response to the manipulation, HIF1A-AS2 expression showed obvious decreases ( Figure 4C ).…”

Section: Resultssupporting

confidence: 79%

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

Shu

Ding

Tang

et al. 2022

Front. Cell Dev. Biol.

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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.

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Section: Resultssupporting

confidence: 79%

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

Shu

Ding

Tang

et al. 2022

Front. Cell Dev. Biol.

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“…ChIP assay was performed as previously described by Xu et al [24]. The cells were transfected and cultured to 85% con uence in a 150-mm dish.…”

Section: Chromatin Immunoprecipitation (Chip-qpcr)mentioning

confidence: 99%

Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression

Tang

Cao

et al. 2023

Preprint

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Backgorund Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8. Methods DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2. Results The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification. Conclusion Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.

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“…DUSP2, as a tumor suppressor gene, is down regulated in tumors. Regulations at the transcriptional and post-transcriptional levels, such as chemical stimulation (13), microRNAs (14)(15)(16)(17), and transcription factors(18) were well studied, however, little is known about the regulation of DUSP2 at the translational or post-translational levels. Previous studies have revealed that DUSP2 could be rapidly induced or cleared intracellularly (13,19).…”

Section: Introductionmentioning

confidence: 99%

CSNK2A1/AKT1 signal axis plays a crucial role in DUSP2-mediated apoptosis in pancreatic cancer

Zhang

Kong

Yang

et al. 2023

Preprint

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Pancreatic cancer is a malignant tumor of the digestive tract with poor prognosis. Dual-specificity phosphatase 2 (DUSP2) is a member of the mitogen-activated protein kinase phosphatase family that is involved in multiple pathophysiological processes. However, its role in pancreatic cancer remains further investigation. The most prominent feature of pancreatic cancer is its hypoxic microenvironment, which plays an important role in tumor progression, drug resistance, and immune evasion. Therefore, we explored the role of DUSP2 by simulating such tumor microenvironment and found that DUSP2 regulated the apoptosis of pancreatic cancer in vitro and in vivo. Mechanistically, DUSP2 competed with AKT1 for binding with casein kinase 2 alpha 1 (CSNK2A1) to inhibit the phosphorylation of AKT1, which played a crucial role in regulating apoptosis. Interestingly, aberrant activation of AKT1 resulted in an increase in the ubiquitin E3 ligase tripartite motif containing 21 (TRIM21), which could bind to and mediate ubiquitination-dependent proteasomal degradation of DUSP2. Taken together, our findings demonstrate a novel signal axis of CSNK2A1/AKT1 in DUSP2 regulating apoptosis and the existence of AKT1/TRIM21 feedback regulation in the degradation of DUSP2 protein in pancreatic cancer for the first time.

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A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia

Cited by 25 publications

References 57 publications

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

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

Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression

CSNK2A1/AKT1 signal axis plays a crucial role in DUSP2-mediated apoptosis in pancreatic cancer

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