Histone deacetylase 6 negatively regulated microRNA-199a-5p induces the occurrence of preeclampsia by targeting VEGFA in vitro

Mei, Zhixiong; Huang, Baoqin; Zhang, Yuan; Qian, Xialiu; Mo, Yujun; Deng, Ni

doi:10.1016/j.biopha.2019.108805

Cited by 14 publications

(3 citation statements)

References 36 publications

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“…The Has-miR-135b-5p regulatory mechanism in hESC decidualization involved the regulation of transcription factor 3 (AFT3) which can promote embryo adhesion in vitro by transcriptionally increasing leukemia inhibitory factor expression in epithelial cells (Cheng et al, 2017); in addition, the knockdown of AFT3 significantly disrupts structural features of decidualized stromal cells . Previous research has also shown that the placental growth factor promotes trophoblast cell invasion by upregulating ATF3 expression and downregulating hsa-miR-199a-5p expression (Mei et al, 2019), which was overexpressed and targeted on PDPN in our study. Hsa-miR-199a-5p stimulates ovarian granulosa cell apoptosis in polycystic ovary syndrome, and its downregulation promotes ovarian granulosa cell viability and inhibits apoptosis, while inducing an increase in serum estradiol (E2) levels and a decrease in serum anti-mullerian hormone levels, luteinizing hormone levels, and follicle-stimulating hormone levels in a polycystic ovarian syndrome rat model (Shao et al, 2020).…”

Section: Discussionsupporting

confidence: 73%

Identification of Key Endometrial MicroRNAs and Their Target Genes Associated With Pathogenesis of Recurrent Implantation Failure by Integrated Bioinformatics Analysis

Shang

Cheng

et al. 2022

Front. Genet.

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Purpose: Recurrent implantation failure (RIF) is an enormous challenge for in vitro fertilization (IVF) clinicians. An understanding of the molecular mechanisms of RIF helps to predict prognosis and develop new therapeutic strategies. The study is designed to identify diagnostic biomarkers for RIF as well as the potential mechanisms underlying RIF by utilizing public databases together with experimental validation.Methods: Two microarray datasets of RIF patients and the healthy control endometrium were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed microRNAs (miRNAs) (DEMs) were identified and their target genes were predicted. Then, we identified differentially expressed genes (DEGs) and selected hub genes through protein-protein interaction (PPI) analyses. Functional enrichment analyses of DEGs and DEMs were conducted. Furthermore, the key DEMs which targeted these hub genes were selected to obtain the key miRNA–target gene network. The key genes in the miRNA-target gene network were validated by a single-cell RNA-sequencing dataset of endometrium from GEO. Finally, we selected two miRNA–target gene pairs for further experimental validation using dual-luciferase assay and quantitative polymerase chain reaction (qPCR).Results: We identified 49 DEMs between RIF patients and the fertile group and found 136,678 target genes. Then, 325 DEGs were totally used to construct the PPI network, and 33 hub genes were selected. Also, 25 DEMs targeted 16 key DEGs were obtained to establish a key miRNA–target gene network, and 16 key DEGs were validated by a single-cell RNA-sequencing dataset. Finally, the target relationship of hsa-miR-199a-5p-PDPN and hsa-miR-4306-PAX2 was verified by dual-luciferase assay, and there were significant differences in the expression of those genes between the RIF and fertile group by PCR (p < 0.05).Conclusion: We constructed miRNA–target gene regulatory networks associated with RIF which provide new insights regarding the underlying pathogenesis of RIF; hsa-miR-199a-5p-PDPN and hsa-miR-4306-PAX2 could be further explored as potential biomarkers for RIF, and their detection in the endometrium could be applied in clinics to estimate the probability of successful embryo transfer.

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Section: Discussionsupporting

confidence: 73%

Identification of Key Endometrial MicroRNAs and Their Target Genes Associated With Pathogenesis of Recurrent Implantation Failure by Integrated Bioinformatics Analysis

Shang

Cheng

et al. 2022

Front. Genet.

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“…VEGFA is a hub node predicted in our study and is found to get downregulated in pre-eclampsia. It was earlier reported to be a direct target for miR-199a-5p, and its expression is decreased in pre-eclampsia (Mei et al, 2019).…”

Section: Discussionmentioning

confidence: 94%

Protein-protein interaction map in pre-eclampsia through the interaction of hub genes, transcription factors and microRNAs

Guttula

Agrawal

Gupta

2022

Preprint

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Pre-eclampsia causes complications in pregnancy and characterized by uremia, proteinuria and hypertension in unattended cases. Blood biomarkers for pre-eclampsia are lacking. In this study, microarray gene expression data from peripheral blood of pre-eclampsia women was analyzed. In our study we developed a combined network approach for hub node prediction regulated by transcription factors and microRNAs corresponding to pre-eclampsia. Differentially expressed genes (DEGs) interaction map was constructed using STRING database. JUN, RPL35, NDUFB2, ATP5I, UQCRQ, COX7C, and FN1 were predicted as potential novel hub genes. Pathway analysis showed metabolic pathways, cytokine signaling in the immune system, Wnt, and MAPK signaling pathways involvement in pre-eclampsia. Regulatory network analysis showed that transcription factors JUN and STAT1 were connected with hub nodes, and microRNAs (miRNAs) like hsa-miR-26b-5p and hsa-miR-155-5p. In conclusion, the expression pattern of hub genes, analyzed deciphers a molecular signature for understanding the pathophysiology of pre-eclampsia and prediction of biomarkers for diagnosis.

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“…For instance, its target gene activating transcription factor 3 (AFT3) promotes embryo adhesion in vitro by transcriptionally increasing leukaemia inhibitory factor expression in epithelial cells [50], and knockdown of this AFT3 signi cantly disrupts structural features of decidualized stromal cells [51]. Previous research has also shown that placental growth factor promotes trophoblast cell invasion by up-regulating ATF3 expression and down-regulating hsa-miR-199a-5p expression [52], which was overexpressed and target on PDPN in our study. Hsa-miR-199a-5p stimulates ovarian granulosa cell apoptosis in polycystic ovary syndrome, and its downregulation promotes ovarian granulosa cell viability and inhibits apoptosis, while induces an increase in serum estradiol (E2) levels and a decrease in serum anti-mullerian hormone levels, luteinizing hormone, and follicle-stimulating hormone levels in a polycystic ovarian syndrome rat model [53].…”

Section: Discussionmentioning

confidence: 99%

Identification of key endometrial microRNAs and its target genes associated with pathogenesis of recurrent implantation failure by integrated bioinformatics analysis

Shang

Cheng²,

Li³

et al. 2022

Preprint

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Purpose Recurrent implantation failure (RIF) is an enormous challenge for In Vitro Fertilization (IVF) clinicians. Understanding of the molecular mechanisms of RIF helps to predict prognosis and develop new therapeutic strategies. The study is designed to identify diagnosis biomarkers for RIF, as well as the potential mechanisms underlying RIF by utilizing public databases together with experimental validation. Methods Two microarray datasets of RIF patients and healthy controls endometrium were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, differentially expressed microRNAs(miRNAs) (DEMs) were identified and their target genes were predicted. Then we identified differentially expressed genes (DEGs) and selected hub genes through Protein-protein interaction (PPI) analyses. Functional enrichment analyses of DEGs and DEMs were conducted. Furthermore, the key DEMs which targeted those hub genes were selected to obtain key miRNA-target genes network. The key genes in miRNA-target genes network were validation by a single cell RNA-sequencing dataset of endometrium from GEO. Finally, we selected two miRNA-target genes pairs to further experimental validation used dual-luciferase assay and quantitative PCR (qPCR). Results We identified 49 DEMs between RIF patients and fertile group and found 136,678 target genes. Then 325 DEGs were totally used to construct PPI network, and 33 hub genes were selected. 25 DEMs targeted 16 key DEGs were obtained to establish key miRNA-target genes network, and 16 key DEGs were validated by single cell RNA-sequencing dataset. Finally, the target relationship of hsa-miR-199a-5p-PDPN and hsa-miR-4306-PAX2 were verified by dual-luciferase assay, and there were significant differences in the expression of those genes between RIF and fertile group by PCR (P<0.05). Conclusion We constructed miRNA-target gene regulatory networks associated with RIF which provide new insights regarding the underlying pathogenesis of RIF. hsa-miR-199a-5p-PDPN, hsa-miR-4306-PAX2 could be further explored as potential biomarkers for RIF, and their detection in endometrium could be applied in clinics to estimate the probability of successful embryo transfer.

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Histone deacetylase 6 negatively regulated microRNA-199a-5p induces the occurrence of preeclampsia by targeting VEGFA in vitro

Cited by 14 publications

References 36 publications

Identification of Key Endometrial MicroRNAs and Their Target Genes Associated With Pathogenesis of Recurrent Implantation Failure by Integrated Bioinformatics Analysis

Identification of Key Endometrial MicroRNAs and Their Target Genes Associated With Pathogenesis of Recurrent Implantation Failure by Integrated Bioinformatics Analysis

Protein-protein interaction map in pre-eclampsia through the interaction of hub genes, transcription factors and microRNAs

Identification of key endometrial microRNAs and its target genes associated with pathogenesis of recurrent implantation failure by integrated bioinformatics analysis

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