AUTHOR=Ismail Mohammed , Zhang Xi , Taha Reham , Elhafiz Muhanad , Zhang Qianwen , Yousef Bashir A. , Huang Xin , Jiang Zhenzhou , Zhang Luyong , Sun Lixin 

TITLE=Expression profiles of lncRNAs and their possible regulatory role in monocrotaline-induced HSOS in rats

JOURNAL=Frontiers in Genetics

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1041266

DOI=10.3389/fgene.2023.1041266

ISSN=1664-8021

ABSTRACT=Aims: Long noncoding RNAs (lncRNAs) have a contribution in the regulation of vital physiological processes and the pathogenesis of many diseases. Monocrotaline (MCT) can cause large-scale outbreaks of toxic liver disease in humans and animals as hepatic sinusoidal obstruction syndrome (HSOS). Although many experiments were performed to explain the pathogenesis, and treatment of MCT-induced HSOS, no studies were conducted on lncRNA roles on it. This research aimed to study the lncRNA-mRNA regulation network in MCT-induced HSOS in rats.
Main methods: We established MCT-induced HSOS, and then carried out microarray for liver tissues of SD rats in an early HSOS model (MCT-12h treated and control groups) to investigate the differentially expressed lncRNAs and mRNAs in the early hepatotoxicity, followed by RT-PCR for selected lncRNAs, which were markedly changed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome analysis were also conducted
Key findings:  176 lncRNAs (63 down-regulated and 113 up-regulated) and 4221 mRNAs (2385 down-regulated and 1836 up-regulated) were differentially expressed in the MCT-treated group compared to the control group. According to biological processes in enriched GO terms, the positive regulation of Guanosine Triphosphate Phosphohydrolase, liver development, and the oxidative-reduction process had roles in hepatotoxicity. Pathway analysis revealed that metabolism pathways, Gap junction, and Ribosome biogenesis in eukaryotes had close relationships with MCT-induced hepatotoxicity. According to analysis, LOC102552718 might play an essential role in the hepatotoxicity mechanism by regulating Inositol 1,4,5-trisphosphate Receptor-1 (Itpr-1) expression.
Significance: This study provides a basis for further research on the molecular mechanisms, and treatment of MCT-induced hepatotoxicity, especially in the early stage, which is pivotal to treat it successfully before irreversible liver damage occurs.