Large-scale quantitative genomics analyzes the circRNA expression profile and identifies the key circRNA in regulating cell proliferation during the proliferation phase of rat LR

Researchers have been exploring the genetic mechanisms underlying the control of liver regeneration (LR). However, an integrated analysis of circRNAs expression of rat regenerating livers during the proliferation phase has not been performed yet. For this purpose, circRNAs expression profile was globally analyzed by high-throughput sequencing. It showed that 10,003 circRNAs were detected, and 164 circRNAs were differentially expressed. Subsequently, 27 circRNAs were predicted to bind to 58 candidate miRNAs and compete for miRNA-binding sites with 2195 mRNAs. By applying GO and KEGG analysis, it was predicted that these circRNAs significantly participated in tissue regeneration, regulation of cell proliferation and Ras, p53, Wnt, Jak-STAT, MAPK signalling pathways. Based on the number of the corresponding miRNAs and their role enriched and reported in cell proliferation of LR or hepatocellular carcinoma, four kinds of circRNAs (circ_03848, circ_08236, circ_13398 and circ_15013) were considered as the key circRNAs. The predicted competing endogenous RNA networks and bioinformatics analysis revealed the potential role of these circRNAs in LR, which would provide useful information for understanding the mechanism of LR.

研究人员长期致力于探索调控肝脏再生（Liver Regeneration, LR）的遗传机制，但目前尚未针对增殖阶段大鼠再生肝脏的环状RNA（circular RNAs, circRNAs）表达情况开展整合分析。为此，本研究通过高通量测序对环状RNA的表达谱进行了全局分析。结果显示，共检测到10003条环状RNA，其中164条呈现差异表达。后续预测发现，27条环状RNA可结合58个候选微小RNA（microRNAs, miRNAs），并与2195条信使RNA（messenger RNAs, mRNAs）竞争微小RNA结合位点。通过基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析，预测得到上述环状RNA显著参与组织再生、细胞增殖调控，以及Ras、p53、Wnt、Jak-STAT、MAPK信号通路。基于对应微小RNA的数量，结合这些环状RNA在肝脏再生或肝细胞癌（hepatocellular carcinoma）细胞增殖过程中经富集得到且已有文献报道的功能，最终筛选出4条关键环状RNA：circ_03848、circ_08236、circ_13398及circ_15013。本研究构建的预测性竞争内源RNA调控网络及生物信息学分析结果，揭示了上述环状RNA在肝脏再生中的潜在作用，可为阐明肝脏再生的调控机制提供重要参考依据。