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

Wenyan Wu; Weifang Wu; Yongqin Ye; Tao Li; Bin Wang

doi:10.3892/etm.2022.11571

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

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

Authors

Wenyan Wu^{1

2}, Weifang Wu^{3

4}, Yongqin Ye^{4

5}, Tao Li², Bin Wang⁴

Affiliations

¹ Medical Laboratory, Shenzhen Luohu People's Hospital, Shenzhen, Guangdong 518001, P.R. China.
² Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong 523000, P.R. China.
³ Medical College, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
⁴ Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong 518026, P.R. China.
⁵ Faculty of Medicine, Macau University of Science and Technology, Macau SAR 999078, P.R. China.

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.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China under (grant no. 81770512), Science, Technology and Innovation Commission of Shenzhen Municipality under (grant no. JCYJ20210324134202007) and Sanming Project of Medicine in Shenzhen under Grant (grant no. SZSM201812055).