Comprehensive circRNA expression profile and hub genes screening during human liver development

Area of Science:

• Genomics
• Developmental Biology
• RNA Biology

Background:

• Non-coding RNAs, specifically circular RNAs (circRNAs), are increasingly recognized for their roles in cellular processes.
• Understanding circRNA expression during human liver development is crucial for insights into liver diseases.

Purpose of the Study:

• To investigate the roles and regulatory networks of circRNAs in human liver development.
• To identify key circRNAs and genes involved in embryonic liver formation.

Main Methods:

• High-throughput sequencing and bioinformatics analysis of human fetal liver samples across developmental stages.
• Differential expression analysis, Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analyses.
• Construction of co-expression and protein-protein interaction (PPI) networks, followed by validation using quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Main Results:

• Identified 645 differentially expressed circRNAs and 5,145 differentially expressed mRNAs.
• circRNA activity was significantly boosted during the hepatoblastic stage, involved in nervous system regulation, embryonic organ development, and digestive system development.
• Key pathways implicated include PI3K-AKT, MAPK, and calcium signaling; three hub genes (LGR5, FOXL1, RSPO3) were identified as potentially crucial for liver development.

Conclusions:

• This study provides the first comprehensive insights into circRNA roles in human liver development.
• Established circRNA regulatory networks and identified key genes, laying the foundation for future research into molecular and signaling networks in liver development and disease.