Abstract
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.
Highlights
Spina bifida is one of the most common central nervous system (CNS) malformations found in fetuses: the neural tube shows incomplete closure, and is usually complicated by other neurological abnormalities and comorbidities such as hydrocephalus
To further validate the results of the microarray analysis, we examined the expression of the three key genes which have dysregulated expression in spina bifida by quantitative real time polymerase chain reaction (qRT-PCR) using spinal cord samples from spina bifida and control fetus with induced labor with non CNS congenital malformations
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
Summary
Spina bifida is one of the most common central nervous system (CNS) malformations found in fetuses: the neural tube shows incomplete closure, and is usually complicated by other neurological abnormalities and comorbidities such as hydrocephalus. Spina bifida can be broadly classified into two groups: spina bifida aperta and spina bifida occulta. The former refers to meninges or nerve. There is no need to treat spina bifida occulta. Spina bifida is often either treated after birth or an intrauterine defect repair is undertaken (Alabi et al, 2018). Complications such as hydrocephalus, fecal dysfunction, voiding dysfunction, and limb mobility disorders cannot be completely avoided. Elucidation of the pathogenesis of spina bifida is urgently required in order to reduce harm to the fetus, as well as that to society and the family
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