Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, P.R. China.
DNA Cell Biol. 2020 Nov;39(11):2059-2076. doi: 10.1089/dna.2020.5750. Epub 2020 Sep 22.
The liver has an excellent capacity for regeneration when faced with external injury and the damage differs from that of other organs in the body. Our aim was to identify the role of circular RNA (circRNA) during the DNA synthesis phase (36 h) of mice liver regeneration. High-throughput RNA sequencing was conducted to explore circRNA and messenger RNA (mRNA) expression in three pairs of mice liver tissue at 0 and 36 h after 2/3 partial hepatectomy. One hundred differentially expressed circRNAs were detected, including 66 upregulated and 34 downregulated circRNAs. We also explored 2483 differentially expressed mRNAs, including 1422 upregulated and 1061 downregulated mRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes indicated that cell cycle regulation, material metabolism, and multiple classical pathways were involved in the DNA synthesis process. A competing endogenous RNA (ceRNA) network containing 5 circRNAs, 28 target genes, and 533 microRNAs (miRNAs) was constructed, and we selected the top 5 miRNAs to map it. Potential key circRNAs were validated with the quantitative real-time PCR technique and their regeneration curves, including consecutive time points, were produced. Finally, a cell counting kit-8 assay on key circRNAs of ceRNA network was performed to further confirm their roles in the DNA synthesis phase of liver regeneration. This study provides a circRNA expression profile for liver regeneration and contributes valuable information for future research.
肝脏在面对外部损伤时有很强的再生能力，其损伤与体内其他器官的损伤不同。我们的目的是鉴定在小鼠肝再生的 DNA 合成阶段（36 小时）circRNA 的作用。通过对 2/3 肝部分切除后 0 小时和 36 小时的 3 对小鼠肝组织进行高通量 RNA 测序，探讨 circRNA 和信使 RNA（mRNA）的表达情况。检测到 100 个差异表达的 circRNA，包括 66 个上调和 34 个下调的 circRNA。我们还探讨了 2483 个差异表达的 mRNAs，包括 1422 个上调和 1061 个下调的 mRNAs。基因本体和京都基因与基因组百科全书表明，细胞周期调控、物质代谢和多种经典途径参与了 DNA 合成过程。构建了一个包含 5 个 circRNA、28 个靶基因和 533 个 microRNAs（miRNAs）的竞争性内源 RNA（ceRNA）网络，我们选择了前 5 个 miRNAs 进行映射。利用定量实时 PCR 技术对潜在关键 circRNAs 进行验证，并绘制其再生曲线，包括连续时间点。最后，对 ceRNA 网络中关键 circRNA 的细胞计数试剂盒-8 检测进一步证实了它们在肝再生 DNA 合成阶段的作用。本研究为肝再生提供了一个 circRNA 表达谱，为未来的研究提供了有价值的信息。
