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MiR-381-3p contribution in mouse spontaneous abortion via targeting VEGFA

ABSTRACT: miR-381-3p contribution in mouse spontaneous abortion via targeting VEGFA

PROVIDER: PRJNA1209548 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31968900.fastq.gz	Fastqsanger.gz
	SRR31968901.fastq.gz	Fastqsanger.gz
	SRR31968902.fastq.gz	Fastqsanger.gz
	SRR31968903.fastq.gz	Fastqsanger.gz
	SRR31968904.fastq.gz	Fastqsanger.gz

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miR-381-3p contribution in mouse spontaneous abortion via targeting VEGFA

Project description:Recurrent spontaneous abortion (RSA) affects 1-5% of pregnant women, yet the mechanisms behind the disease remain unknown. It is well acknowledged that insufficient blood flow and placental abnormalities are key factors contributing to RSA. The abortive mouse model was constructed by intraperitoneal injection of β2-GPI. miRNA expression profiles in placental tissues of aborted and normal pregnant mice were detected by high-throughput sequencing. We found that miR-381-3p was highly expressed in the placenta of aborted mice and may bind to VEGFA

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Expression of miR-381-3p is elevated in the retina of OIR mice, but the role in the retinal neovascularization is elusive，and its mechanism of action was investigated by vitreous injection of miR-381-3p antagomir

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Epigenome analysis of decidua tissues from unexplained recurrent spontaneous abortion patients and controls with induced abortions

Project description:Genome wide DNA methylation profiling of decidua samples from unexplained recurrent spontaneous abortion patients and controls with induced abortions. The Infinium Human Methylation 850K BeadChip was used to obtain DNA methylation profiles across approximately 853,307 CpGs in decidua samples . Samples included 2 normal pregnant women (non-medical reasons for abortion) and 4 unexplained recurrent spontaneous abortion patients.

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Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk

Project description:Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.

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ADAR1 controls the miR-381-3p-mediated expression of MRP4 by regulating the production of circHIPK3 in human renal cell

Project description:Multidrug resistance-associated protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is highly expressed in the kidney of mammals and responsible for renal elimination of various drugs. Adenosine deaminase acting on RNA 1 (ADAR1) has been reported to regulate gene expression through catalyzing adenosine-to-inosine (A-to-I) RNA editing. In this study, we found that the down-regulation of ADAR1 increased the expression of MRP4 in human renal cells at post-transcriptional level. The results of luciferase reporter assays and microarray analysis revealed that down-regulation of ADAR1 decreased the levels of miR-381-3p, which led to the up-regulation of MPR4 expression. Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs that play a critical role of gene expression by acting as miRNA sponges. ADAR1 repressed the biogenesis of circular RNA circHIPK3 by catalyzing A-to-I RNA editing, which changed the secondary structure of precursor of circHIPK3. In silico analysis suggested that circHIPK3 acted as a sponge of miR-381-3p. Indeed, overexpression of circHIPK3 up-regulated the expression of MRP4 through interfering with miR-381-3p. Our results provide the novel point of view for regulating mechanism of the expression of xenobiotic transporters through mediating the control of circRNA expression by RNA editing enzyme ADAR1.

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