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. 2022 Aug 22;24(4):634.
doi: 10.3892/etm.2022.11571. eCollection 2022 Oct.

mRNA and lncRNA expression profiles of liver tissues in children with biliary atresia

Wenyan Wu  1   2 , Weifang Wu  3   4 , Yongqin Ye  4   5 , Tao Li  2 , Bin Wang  4
Affiliations

mRNA and lncRNA expression profiles of liver tissues in children with biliary atresia

Wenyan Wu et al. Exp Ther Med. .

Abstract

Progressive liver fibrosis is the most common phenotype in biliary atresia (BA). A number of pathways contribute to the fibrosis process so comprehensive understanding the mechanisms of liver fibrosis in BA will pave the way to improve patient's outcome after operation. In this study, the differentially expressed profiles of mRNAs and long non-coding RNAs from BA and choledochal cyst (CC) liver tissues were investigated and analyzed, which may provide potential clues to clarify hepatofibrosis mechanism in BA. A total of two BA and two CC liver tissue specimens were collected, the expression level of mRNAs and lncRNAs was detected by RNA sequencing. Differentially expressed mRNAs (DEmRNAs) were functionally annotated and protein-protein interaction networks (PPI) was established to predict the biological roles and interactive relationships. Differentially expressed lncRNAs (DElncRNAs) nearby targeted DEmRNA network and DElncRNA-DEmRNA co-expression network were constructed to further explore the roles of DElncRNAs in BA pathogenesis. The expression profiles of significant DEmRNAs were validated in Gene Expression Omnibus database. A total of 2,086 DEmRNAs and 184 DElncRNAs between BA and CC liver tissues were obtained. DEmRNAs were enriched in 521 Gene Ontology terms and 71 Kyoto Encyclopedia of Genes and Genomes terms which were mainly biological processes and metabolic pathways related to immune response and inflammatory response. A total of five hub proteins (TYRO protein tyrosine kinase binding protein, C-X-C motif chemokine ligand 8, pleckstrin, Toll-like receptor 8 and C-C motif chemokine receptor 5) were found in the PPI networks. A total of 31 DElncRNA-nearby-targeted DEmRNA pairs and 2,337 DElncRNA-DEmRNA co-expression pairs were obtained. The expression of DEmRNAs obtained from RNA sequencing were verified in GSE46960 dataset, generally. The present study identified key genes and lncRNAs participated in BA associated liver fibrosis, which may present a new avenue for understanding the patho-mechanism for hepatic fibrosis in BA.

Keywords: biliary atresia; bioinformation analysis; liver fibrosis; long non-coding RNA; mRNA.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
DEmRNAs and DElncRNAs between BA liver tissues and CC liver tissues. Volcano spot results of (A) DEmRNAs and (B) DElncRNAs between BA liver tissues and CC liver tissues. Red spot and green spot respectively indicated up- and downregulated genes, blue spot indicated no significant difference. Hierarchical clustering results of (C) DEmRNAs and (D) DElncRNAs between BA liver tissues and CC liver tissues. DEmRNAs/DElncRNAs and tissue samples were displayed as row and column, respectively. The color scale represented the expression levels. DEmRNAs, differentially expressed mRNAs; DElncRNAs, differentially expressed lncRNAs; BA, biliary atresia; CC, choledochal cyst.
Figure 2
Figure 2
Top 20 significantly enriched GO terms and top 20 KEGG pathways of DEmRNAs between BA liver tissues and CC liver tissues. The x-axis is p-value for each GO term or pathway as -log10 and the y-axis indicates (A) biological process GO term, (B) cellular component GO term, (C) molecular function GO term or (D) KEGG pathway. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; DEmRNAs, differentially expressed mRNAs; BA, biliary atresia; CC, choledochal cyst.
Figure 3
Figure 3
PPI networks. Proteins encoded by up- and downregulated DEmRNAs between BA liver tissues and CC liver tissues were displayed as red and green ellipses. DEmRNAs derived from top 10 up- and downregulated DEmRNAs between BA liver tissues and CC liver tissues were displayed in ellipses with a black border. PPI, protein-protein interaction; DEmRNAs, differentially expressed mRNAs; BA, biliary atresia; CC, choledochal cyst.
Figure 4
Figure 4
DElncRNA-nearby DEmRNA interaction networks. DElncRNAs and their nearby DEmRNAs between BA liver tissues and CC liver tissues, respectively, were represented in the rhombus and ellipses. up- and downregulation of DEmRNAs in BA liver tissues compared with CC were shown in red and green color, respectively. DElncRNAs/DEmRNAs derived from top 10 up- and downregulated DElncRNAs/DEmRNAs were displayed in rhombus and ellipses with a black border. DElncRNAs, differentially expressed lncRNAs; DEmRNAs, differentially expressed mRNAs; BA, biliary atresia; CC, choledochal cyst.
Figure 5
Figure 5
DElncRNA-DEmRNA co-expression networks, including (A) positive regulatory and negative regulated networks. (B and C). DElncRNAs and their nearby DEmRNAs between BA liver tissues and CC liver tissues were shown in triangles and ellipses, respectively. Up- and downregulation in BA liver tissues compared with CC liver tissues were displayed in red and green color, respectively. DElncRNAs/DEmRNAs derived from top 10 up- and downregulated DElncRNAs/DEmRNAs were displayed in triangles and ellipses with a black border. DElncRNAs, differentially expressed lncRNAs; DEmRNAs, differentially expressed mRNAs; BA, biliary atresia; CC, choledochal cyst.
Figure 6
Figure 6
Top 20 significantly enriched GO terms and KEGG pathways of DEmRNAs co-expressed with DElncRNAs between BA liver tissues and CC liver tissues. The x-axis is P-value for each GO term or pathway as -log10 and the y-axis indicates (A) biological process GO term, (B) cellular component GO term, (C) molecular function GO term or (D) KEGG pathway. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; DEmRNAs, differentially expressed mRNAs; BA, biliary atresia; CC, choledochal cyst.
Figure 7
Figure 7
Validation of selected DEmRNAs in GEO database. Venn diagrams indicating that (A) 111 upregulated and (B) 102 downregulated DEmRNAs were consistently in both expression profiles. Boxplot showed (C) 5 upregulated DEmRNAs and (D) 6 downregulated DEmRNAs expression patterns; GEO, Gene Expression Omnibus.
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