miR‐322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4

Liu, Yusi; Gu, Hui; Huang, Tzung-Chi; Wei, Xiaowei; Ma, Wei; Liú, Dan; He, Yiwen; Luo, Wenting; Huang, Jieting; Zhao, Duan; Jia, Shanshan; Wang, Fang; Zhang, Ting; Bai, Yuling; Wang, Wei‐lin; Yuan, Zhengwei

doi:10.1111/cns.13383

Cited by 14 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, our research group has been devoted to the study of the genetic and epigenetic etiology and pathogenesis of spina bifida ( Fan et al, 2011 ; Shan et al, 2012 ; Wei et al, 2013 ; Zhang H. et al, 2019 ; Zhang H.N. et al, 2019 ; An et al, 2020 ; Liu et al, 2020 ), as well as the diagnosis and prenatal diagnosis of diseases ( Gu et al, 2012 ; An et al, 2015 ), gene therapy ( Ma et al, 2020 ) and stem cell therapy ( Li et al, 2012 ; Wei et al, 2020a,b ) and other etiological treatments, which are conducive to improving the level of disease prevention and treatment. However, we still believe more needs to be done.…”

Section: Discussionmentioning

confidence: 99%

Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida

Feng

Yuan

2020

Front. Genet.

View full text Add to dashboard Cite

Spina bifida is a common neural tube defect (NTD) accounting for 5–10% of perinatal mortalities. As a polygenic disease, spina bifida is caused by a combination of genetic and environmental factors, for which the precise molecular pathogenesis is still not systemically understood. In the present study, we aimed to identify the related gene module that might play a vital role in the occurrence and development of spina bifida by using weighted gene co-expression network analysis (WGCNA). Transcription profiling according to an array of human amniocytes from patients with spina bifida and healthy controls was downloaded from the Gene Expression Omnibus database. First, outliers were identified and removed by principal component analysis (PCA) and sample clustering. Then, genes in the top 25% of variance in the GSE4182 dataset were then determined in order to explore candidate genes in potential hub modules using WGCNA. After data preprocessing, 5407 genes were obtained for further WGCNA. Highly correlated genes were divided into nineteen modules. Combined with a co-expression network and significant differentially expressed genes, 967 candidate genes were identified that may be involved in the pathological processes of spina bifida. Combined with our previous microRNA (miRNA) microarray results, we constructed an miRNA–mRNA network including four miRNAs and 39 mRNA among which three key genes were, respectively, linked to two miRNA-associated gene networks. Following the verification of qRT-PCR and KCND3 was upregulated in the spina bifida. KCND3 and its related miR-765 and miR-142-3p are worthy of further study. These findings may be conducive for early detection and intervention in spina bifida, as well as be of great significance to pregnant women and clinical staff.

show abstract

Section: Discussionmentioning

confidence: 99%

Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida

Feng

Yuan

2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Intriguingly, some mechanisms that lead to elevated apoptotic levels in excess ATRA conditions and diabetic conditions involve common molecular players. One mechanism leading to the increased incidence of apoptosis in excess ATRA conditions is by way of repression of miR-322 and enrichment of the NADPH oxidase NOX4 (Figure 1-green) (Y.-S. Liu et al, 2020). How NOX4 induces apoptosis is unknown.…”

Section: Retinoic Acidmentioning

confidence: 99%

“…How NOX4 induces apoptosis is unknown. Impressively, injection of a miR-322 mimic into an ATRA treated mouse prevented both the increase in apoptosis and NTD phenotype (Y.-S. Liu et al, 2020). Alternatively, miR-322 is also a known repressor of TRAF3 and in the diabetic mouse model or in high glucose cultured cells, miR-322 expression is reduced and TRAF3 expression is enriched resulting in an increase in apoptotic cells (Figure 1-purple) (Gu et al, 2015).…”

Section: Retinoic Acidmentioning

confidence: 99%

“…In these cases, an increase in apoptosis is found in varying regions of the neural tube based on the type of micronutrient imbalance. ATRA-induced NTDs in mice and rats often result in caudal NTDs and the incidence of apoptosis is increased in that area (Figure 1-green) (Y.-S. Liu et al, 2020;Wei et al, 2012). In contrast, zinc deficiency by TPEN results in cranial NTDs accompanied by an increase in apoptosis in the cranial neural tube (Figure 1-yellow) .…”

Section: Apoptosis As a Central Phenotype In Ntdsmentioning

confidence: 99%

“…MiRNAs have also been implicated in several multifactorial neurodevelopmental disorders such as Fragile X syndrome, Rett syndrome, and autism spectrum disorder (Ardekani & Naeini, 2010). In mouse and rat, it has been reported that miRNAs are dysregulated in NTDs induced by ATRA, p53 null mutation, and STZ (diabetic model) suggesting that miRNA dysregulation is common to NTDs arising from different environmental factors (Gu et al, 2015, p. 322;Hosako et al, 2009;Y.-S. Liu et al, 2020). Furthermore, sequencing in human NTD and control cases revealed six miRNAs that were enriched during pregnancy in maternal serum from mothers carrying a fetus with an NTD (Gu et al, 2012).…”

Section: Hierarchical Nodes: Dysregulation Of Ddr and Mirnas As Root Causes For Ntdmentioning

confidence: 99%

See 2 more Smart Citations

Micronutrient imbalance and common phenotypes in neural tube defects

Kakebeen

Niswander

2021

Genesis

View full text Add to dashboard Cite

Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex involving the interplay of genetic and environmental factors. Since nutrient deficiency is a risk factor and dietary changes are the major preventative measure to reduce the risk of NTDs, a more detailed understanding of how common micronutrient imbalances contribute to NTDs is crucial. While folic acid has been the most discussed environmental factor due to the success that population-wide fortification has had on prevention of NTDs, folic acid supplementation does not prevent all NTDs. The imbalance of several other micronutrients has been implicated as risks for NTDs by epidemiological studies and in vivo studies in animal models. In this review, we highlight recent literature deciphering the multifactorial mechanisms underlying NTDs with an emphasis on mouse and human data. Specifically, we focus on advances in our understanding of how too much or too little retinoic acid, zinc, and iron alter gene expression and cellular processes contributing to the pathobiology of NTDs. Synthesis of the discussed literature reveals common cellular phenotypes found in embryos with NTDs resulting from several micronutrient imbalances. The goal is to combine knowledge of these common cellular phenotypes with mechanisms underlying micronutrient imbalances to provide insights into possible new targets for preventative measures against NTDs.

show abstract

HIF‐1α‐induced upregulated miR‐322 forms a feedback loop by targeting Smurf2 and Smad7 to activate Smad3/β‐catenin/HIF‐1α, thereby improving myocardial ischemia‐reperfusion injury

Wang

Dong

Zhu

et al. 2023

Cell Biology International

View full text Add to dashboard Cite

Myocardial ischemia/reperfusion injury (MIRI) is a major cause of heart failure after myocardial infarction. It has been reported that miR‐322 is involved in MIRI progression, while the molecular mechanism of miR‐322 in regulating MIRI progression needs to be further probed. MIRI cell model was established by oxygen‐glucose deprivation/reoxygenation (OGD/R). Cell viability was assessed using MTS assay. Flow cytometry and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining were employed to analyze cell apoptosis. In addition, the interactions between miR‐322, Smad7/Smurf2, hypoxia‐inducible factor alpha (HIF‐1α), and β‐catenin were verified by dual‐luciferase reporter gene assay. Our results displayed that miR‐322 was significantly downregulated in OGD/R‐treated H9c2 cells, and its overexpression resulted in increased cell viability and reduced the apoptosis. Smurf2 and Smad7 were identified as the direct targets of miR‐322. Smad7 knockdown or Smurf2 knockdown increased OGD/R‐treated H9c2 cell viability and suppressed the apoptosis. Meanwhile, miR‐322 mimics abolished the mitigating effect of Smad7 or Smurf2 overexpression on MIRI. In addition, the Smad3/β‐catenin pathway was identified as the downstream pathway of Smurf2/Smad7. Moreover, it was found that HIF‐1α interacted with the miR‐322 promoter, and β‐catenin interacted with the HIF‐1α promoter to form a loop. HIF‐1α‐induced upregulated miR‐322 activated the Smad3/β‐catenin pathway by targeting Smurf2 and Smad7 to improve MIRI; meanwhile, β‐catenin/HIF‐1α formed a positive feedback loop to continuously improve MIRI.

show abstract

miR‐322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4

Cited by 14 publications

References 41 publications

Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida

Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida

Micronutrient imbalance and common phenotypes in neural tube defects

HIF‐1α‐induced upregulated miR‐322 forms a feedback loop by targeting Smurf2 and Smad7 to activate Smad3/β‐catenin/HIF‐1α, thereby improving myocardial ischemia‐reperfusion injury

Contact Info

Product

Resources

About