Study On The Ways And Means Of Highly Expressed Lncrnas In Regulating Hepatocyte Proliferation During Rat Liver Regeneration

In this study, we used high-throughput sequencing method to detect lncRNAs expressed in hepatocytes during 2/3 hepatectomy induced rat liver regeneration at 10 time points and screened the highly expressed lncRNAs according to their expression abundance. The results showed that 11,389 lncRNAs were expressed in hepatocytes during rat liver regeneration, of which 130 lncRNAs were highly expressed with abundance above 100.To understand the role of these highly expressed lncRNAs in liver regeneration,bioinformatics method was used to predict their target genes. The results showed that the 130 highly expressed lncRNAs were aimed at 1314 target genes. To further screen lncRNAs to be studied and understand their roles in liver regeneration, based on their target genes we used Rat Genome 230 2.0 Array to determine expression changes of the 1314 target genes in hepatocytes during 2/3 hepatectomy induced rat liver regeneration at 10 time points. The result showed that 751 of the target genes were detected, and 243 were significantly changed.Of them, 175 were significantly up-regulated, 66 were significantly down-regulated and 2were up/down-regulated. Physiological activities analysis of these 243 significant-expressed target genes indicated that 238 of them have known functions; they are mainly involved in stimulus reaction, developmental process, cell communication, signal transduction, nucleic acid metabolic process, organ development, transport, cell proliferation and cell differentiation; 68 of them participated in cell proliferation.We selected cell proliferation to further study the ways and means of highly expressed lncRNAs to regulate liver regeneration through their significant-expressed target genes.Signaling pathways of the 243 significant-expressed target genes were confirmed using the method established by our group; the results showed that they are involved in 15 cell proliferation-related signaling pathways. Spectral function Ep(t) was used to analyzesignaling activities of the 15 cell proliferation-related signaling pathways. The result indicated that 6 of them were activated in the initiation and/or progression phase during rat liver regeneration including Growth Hormone, NF-κB, PI3K/AKT, HGF, IL-6 and cAMP signaling pathways. Further synergy effect analysis of the above 68 cell proliferation-related target genes showed that the cell proliferation activity dominated by them was activated in the progression phase during rat liver regeneration. The results indicated that signaling activities of cell proliferation-related signaling pathways dominated by significant-expressed target genes of highly expressed lncRNAs and cell proliferation activities dominated by significant-expressed target genes were positively correlated.The above results suggested that Growth Hormone, NF-κB, PI3K/AKT, HGF, IL-6 and cAMP signaling pathways enriched by significant-expressed target genes of highly expressed lncRNAs promoted hepatocytes proliferation during rat liver regeneration. 9 lncRNAs were involved in the 6 signaling pathways. This study added insight about gene expression regulatory networks in rat liver regeneration and provided information for further elucidating mechanisms of rat liver regeneration.