Li Lifei, Guo Jianlin, Chen Yanhui, Chang Cuifang, Xu Cunshuan
College of Life Science, Henan Normal University, Xinxiang, 453007, Henan Province, China.
State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, Xinxiang, 453007, Henan Province, China.
BMC Genomics. 2017 Jan 13;18(1):80. doi: 10.1186/s12864-016-3476-6.
Rat liver regeneration (LR) proceeds along a process of highly organized and ordered tissue growth in response to the loss or injury of liver tissue, during which many physiological processes may play important roles. The molecular mechanism of hepatocyte proliferation, energy metabolism and substance metabolism during rat LR had been elucidated. Further, the correlation of circular RNA (circRNA) abundance with proliferation has recently been clarified. However, the regulatory capacity of circRNA in rat LR remains a fascinating topic.
To investigate the regulatory mechanism of circRNA during priming phase of rat LR, high-throughput RNA sequencing technology was performed to unbiasedly profile the expression of circRNA during priming phase of rat LR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis was conducted to predict the functions of differentially expressed circRNAs and their host linear transcripts. Co-expression networks of circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed LR-related circRNAs and the condition of their miRNA binding sites. To excavate the key circRNAs in the early phase of rat LR, we comprehensively evaluated and integrated the relationship of expression level between the circRNAs and the linear transcripts as well as the distribution of miRNA binding sites in circRNA sequences.
This paper is the first to employ the comprehensive circRNA expression profile and to investigate circRNA-miRNA interactions during priming phase of rat LR. Two thousand four hundred twelve circRNAs were detected, and 159 circRNAs deriving from 116 host linear transcripts differentially expressed (p < 0.05). Six significantly changed circRNAs during priming phase of rat LR were screened as key circle molecules, and then were validated by qRT-PCR. This study will lay the foundation for revealing the functional roles of circRNAs during rat LR and help solve the remaining clinical problems.
大鼠肝脏再生（LR）是一个高度组织化且有序的组织生长过程，以应对肝组织的丢失或损伤，在此过程中许多生理过程可能发挥重要作用。大鼠肝脏再生过程中肝细胞增殖、能量代谢和物质代谢的分子机制已得到阐明。此外，环状RNA（circRNA）丰度与增殖之间的相关性最近也已明确。然而，circRNA在大鼠肝脏再生中的调控能力仍是一个引人关注的话题。
为了研究circRNA在大鼠肝脏再生启动阶段的调控机制，采用高通量RNA测序技术对大鼠肝脏再生启动阶段的circRNA表达进行无偏分析。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）生物途径分析，以预测差异表达的circRNA及其宿主线性转录本的功能。基于差异表达的肝脏再生相关circRNA与其miRNA结合位点情况的相关性分析，构建circRNA-miRNA共表达网络。为挖掘大鼠肝脏再生早期的关键circRNA，我们综合评估并整合了circRNA与线性转录本之间的表达水平关系以及circRNA序列中miRNA结合位点的分布。
本文首次采用全面的circRNA表达谱，并研究大鼠肝脏再生启动阶段的circRNA-miRNA相互作用。共检测到2412个circRNA，其中116个宿主线性转录本来源的159个circRNA差异表达（p < 0.05）。筛选出大鼠肝脏再生启动阶段6个显著变化的circRNA作为关键环状分子，随后通过qRT-PCR进行验证。本研究将为揭示circRNA在大鼠肝脏再生过程中的功能作用奠定基础，并有助于解决剩余的临床问题。
