Dataset Information

Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

ABSTRACT: Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants caused by multifactorial etiology. Genetic factors are involved in the occurrence of BPD, but studies have found that candidate genes have poor reproducibility and are influenced by ethnic heterogeneity; therefore, more exploration is still needed. We performed whole-exon sequencing in 34 preterm infants with BPD and 32 non-BPD control neonates. The data were analyzed and interpreted by Fisher difference comparison, PLINK and eQTL association analysis, KEGG and GO enrichment analysis, STRING tool, Cytoscape software, ProtParam tool, HOPE online software, and GEOR2 analysis on NCBI GEO dataset. BPD has a highly heterogeneity in different populations, and we found 35 genes overlapped with previous whole-exon sequencing studies, such as APOB gene. Arterial and epithelial cell development and energy metabolism pathways affect BPD. In this study, 24 key genes were identified, and BIVM rs3825519 mutation leads to prolonged assisted ventilation in patients with BPD. A novel DDAH1 mutation site (NM_012137: exon1: c.89 T > G: p.L30R) was found in 9 BPD patients.

Conclusion

BIVM gene rs3825519 mutation may play a role in the pathogenesis of BPD by affecting cilia movement, and the DDAH1 and APOB genes mutations may have a pathogenic role in BPD.

What is known

• Genetic factors are involved in the occurrence of bronchopulmonary dysplasia. • The candidate genes have poor reproducibility and are influenced by ethnic heterogeneity, therefore, more exploration is still needed.

What is new

• We identified the role of susceptible SNPs in BPD in Shenzhen, China, and identified 24 key genes that influence the pathogenesis of BPD, and also found 35 genes overlapped with previous whole exon sequencing studies, such as APOB gene. • We found that BIVM and DDAH1 genes may play a pathogenic role in the pathogenesis of BPD.

SUBMITTER: Luo X

PROVIDER: S-EPMC10167099 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

Luo Xi X Zhao Min M Chen Cheng C Lin Fengji F Li Xiaodong X Huang Haiyun H Dou Lei L Feng Jinxing J Xiao Shanqiu S Liu Dong D He Junli J Yu Jialin J

European journal of pediatrics 20230209 4

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants caused by multifactorial etiology. Genetic factors are involved in the occurrence of BPD, but studies have found that candidate genes have poor reproducibility and are influenced by ethnic heterogeneity; therefore, more exploration is still needed. We performed whole-exon sequencing in 34 preterm infants with BPD and 32 non-BPD control neonates. The data were analyzed and interpreted by Fisher difference ...[more]

PMID: 36757497

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Project description:Bronchopulmonary dysplasia (BPD) represents a multifactorial chronic pulmonary pathology and a major factor causing premature illness and death. The therapeutic role of exosomes in BPD has been feverishly investigated. Meanwhile, the potential roles of exosomal circRNAs, lncRNAs, and mRNAs in umbilical cord blood (UCB) serum have not been studied. This study aimed to detect the expression profiles of circRNAs, lncRNAs, and mRNAs in UCB-derived exosomes of infants with BPD. Microarray analysis was performed to compare the RNA profiles of UCB-derived exosomes of a preterm newborn with (BPD group) and without (non-BPD, NBPD group) BPD. Then, circRNA/lncRNA-miRNA-mRNA co-expression networks were built to determine their association with BPD. In addition, cell counting kit-8 (CCK-8) assay was used to evaluate the proliferation of lipopolysaccharide (LPS)-induced human bronchial epithelial cells (BEAS-2B cells) and human umbilical vein endothelial cells (HUVECs). The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in LPS-induced BEAS-2B cells and HUVECs were assessed through Western blot analysis. Then, quantitative reverse transcription-polymerase chain reaction assay was used to evaluate the expression levels of four differentially expressed circRNAs (hsa_circ_0086913, hsa_circ_0049170, hsa_circ_0087059, and hsa_circ_0065188) and two lncRNAs (small nucleolar RNA host gene 20 (SNHG20) and LINC00582) detected in LPS-induced BEAS-2B cells or HUVECs. A total of 317 circRNAs, 104 lncRNAs, and 135 mRNAs showed significant differential expression in UCB-derived exosomes of preterm infants with BPD compared with those with NBPD. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to examine differentially expressed exosomal circRNAs, lncRNAs, and mRNAs. The results showed that the GO terms and KEGG pathways mostly involving differentially expressed exosomal RNAs were closely associated with endothelial or epithelial cell development. In vitro, CCK-8 and Western blot assays revealed that LPS remarkably inhibited the viability and promoted inflammatory responses (TNF-α and IL-1β) of BEAS-2B cells or HUVECs. The expression levels of circRNAs hsa_circ_0049170 and hsa_circ_0087059 were upregulated in LPS-induced BEAS-2B cells; the expression level of hsa_circ_0086913 was upregulated and that of hsa_circ_0065188 was downregulated in LPS-induced HUVECs. Moreover, the expression level of lncRNA SNHG20 was upregulated and that of LINC00582 was downregulated in LPS-induced BEAS-2B cells. Further, 455 circRNA/lncRNA-miRNA-mRNA interaction networks were predicted, including hsa_circ_0086913/hsa-miR-103a-3p/transmembrane 4 L six family member 1 (TM4SF1) and lncRNA-SNHG20/hsa-miR-6720-5p/spermine synthase (SMS) networks, which may take part in BPD.ConclusionThis study provided a systematic perspective on UCB-derived exosomal circRNAs and lncRNAs and laid an important foundation for further investigating the potential biological functions of exosomal circRNAs and lncRNAs in BPD.What is known• BPD represents a multifactorial chronic pulmonary pathology and a major factor causing premature illness and death. • The therapeutic role of exosomes in BPD has been feverishly investigated, and exosomal RNAs were ignored.What is new• The profiles of UCB-derived exosomal circRNAs, lncRNAs, and mRNAs were performed. • Several differentially expressed circRNAs and lncRNAs were identified in LPS-induced BEAS-2B cells and HUVECs.

Project description:BackgroundThe chronic lung condition known as bronchopulmonary dysplasia (BPD), which primarily affects newborns, especially preterm neonates, is brought on by prolonged oxygen consumption and mechanical ventilation. This case-control study sought to investigate the pathogenesis of BPD in preterm neonates by RNA sequencing (RNA-seq).MethodsFirst, RNA-seq samples were collected from 3 BPD and 3 healthy preterm neonates. Based on the sequencing data and microarray data sets, MERGE.57185.1, the key long non-coding RNA (lncRNA), was identified from the differentially expressed lncRNAs and the key module by a weighted gene co-expression network analysis (WGCNA), a Venn diagram, and an expression analysis. Next, the differentially expressed messenger RNAs (mRNAs) and microRNAs (miRNAs) that were strongly correlated to MERGE.57185.1 were identified in the protein-protein interaction networks and underwent a functional enrichment analysis and Spearman correlation analysis. Finally, the mRNA [i.e., eukaryotic translation initiation factor 5A (EIF5A)] and miRNA (i.e., hsa-miR-6833-5p) with the strongest correlations to MERGE.57185.1 were identified as the downstream targets.ResultsAmong the 32 genes in the dark-red module and the 158 differentially expressed lncRNAs, 21 overlapping genes were identified. In the gene expression analysis, MERGE.57185.1 (an oncogene) was identified as the key lncRNA in BPD. The results of the multiple bioinformatics analysis showed that the mRNA and the miRNA with the strongest correlations to MERGE.57185.1 were hsa-miR-6833-5p (a suppressor gene) and EIF5A (an oncogene), respectively. Hsa-miR-6833-5p was lowly expressed in the BPD group, while EIF5A was highly expressed in the BPD group.ConclusionsThis study identified 1 key upregulated lncRNA (i.e., MERGE.57185.1) in preterm neonatal BPD, and revealed the MERGE.57185.1/hsa-miR-6833-5p/EIF5A mechanism in preterm neonatal BPD from the lncRNA-miRNA-mRNA network. This key lncRNA gene could serve as a promising diagnostic biomarker for prenatal examinations.

Dataset Information

Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

Conclusion

What is known

What is new

Publications

Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

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