Identifying the Key Genes in Mouse Liver Regeneration After Partial Hepatectomy by Bioinformatics Analysis and in vitro/ vivo Experiments

Jian Zhao; Shi-Zhe Yu; Qiang Cai; Duo Ma; Long Jiang; Ling-Peng Yang; Zhi-Yong Yu

doi:10.3389/fgene.2021.670706

Identifying the Key Genes in Mouse Liver Regeneration After Partial Hepatectomy by Bioinformatics Analysis and in vitro/ vivo Experiments

Front Genet. 2021 Jun 23:12:670706. doi: 10.3389/fgene.2021.670706. eCollection 2021.

Authors

Jian Zhao¹, Shi-Zhe Yu², Qiang Cai¹, Duo Ma¹, Long Jiang¹, Ling-Peng Yang¹, Zhi-Yong Yu¹

Affiliations

¹ Department of Hepatobiliary Surgery, The Affiliated Hospital of Yunnan University, Kunming, China.
² Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: The liver is the only organ that can completely regenerate after various injuries or tissue loss. There are still a large number of gene functions in liver regeneration that have not been explored. This study aimed to identify key genes in the early stage of liver regeneration in mice after partial hepatectomy (PH).

Materials and methods: We first analyzed the expression profiles of genes in mouse liver at 48 and 72 h after PH from Gene Expression Omnibus (GEO) database. Gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analysis were performed to identify key genes in liver regeneration. Finally, we validated key genes in vivo and in vitro.

Results: We identified 46 upregulated genes and 19 downregulated genes at 48 h after PH, and 223 upregulated genes and 40 downregulated genes at 72 h after PH, respectively. These genes were mainly involved in cell cycle, DNA replication, and p53 signaling pathway. Among of these genes, cycle-related genes (Ccna2, Cdkn1a, Chek1, and Mcm5) and Ube2c were highly expressed in the residual liver both at 48 and 72 h after PH. Furthermore, Ube2c knockdown not only caused abnormal expression of Ccna2, Cdkn1a, Chek1, and Mcm5, but also inhibited transition of hepatocytes from G1 to S phase of the cell cycle in vitro.

Conclusion: Mouse hepatocytes enter the proliferation phase at 48 h after PH. Ube2c may mediate cell proliferation by regulating or partially regulating Ccna2, Cdkn1a, Chek1, and Mcm5.

Keywords: DNA replication; UBE2C; cell cycle; liver regeneration; partial hepatectomy.