Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.

Objective To explore the role pathway and pattern of the sex determining region box transcription factor 2 (SOX2) and its mRNA interaction with microRNA(miRNAs, miR) and circular RNA(circRNA) at 0 hour and 2 hours in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNAs(ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and 2 hours after PH, the ratio value of SOX2 mRNA shows 1.00±0.09 and 2.15±0.48, miR-3558-3p displays 4.53± 0.10 and 0.81±0.16, circRNA_18404 shows 1.24±0.04 and 11.10±0.57, circRNA_18045 displays 1.97±0.47 and 4.44± 0.23. At the same time, the eight kinds of cell dedifferentiation-related genes AT-rich interaction domain 5A (ARID5A), activating transcription factor 3 (ATF3), BTG anti-proliferation factor 2 (BTG2), etc, which are prometed in expression by SOX2, were down-regulated at 0 h after PH, but the cell differentiation-related genes interferon regulatory factor 6 (IRF6) and somatostatin (SST), which are inhibited in expression by SOX2, were up-regulated at 0 hour after PH. On the other hand, the eight kinds of cell dedifferentiation-related genes ARID5A, ATF3, BTG2, etc, which are promoted in expression by SOX2, were up-regulated at 2 hours after PH, but the cell differentiation-related gene SST, which is inhibited in expression by SOX2, was down-regulated, and IRF6 had no meaningful changes in expression at 2 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNA, SOX2, its mRNA is inhibited by miRNA, and the cell stem-related genes, which are regulated by SOX2, are helpful for the hepatocyte to be in differentiation state at 0 hour after PH and to be in stem state at 2 hours after PH.

MicroRNAs (miRNAs, miR) are endogenous non-coding single-stranded RNAs with a length of about 22 nucleotides. These RNAs play an important biological function within cells, among which, miR-429 has been proved to play an important role in inhibiting tumor development and tumor progression as well as in cell differentiation and neurological diseases by regulating the expression of different target genes. In this paper, the role of miR-429 and its downstream targeted genes in cell proliferation, apoptosis, migration and invasion is summarized.

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein δ (CEBPδ) mRNA, miR-3553 and rno-Acad8_0002 regulate the hepatocytes in G

Objective To explore the pathways and patterns which CCAAT enhancer binding proteina (CEBPα) mRNA, miR-144-3p, rno-LOC100365958_0001, rno-Usp3_0010 and rno-AC241873_0010 regulate the hepatocytes in G

Objective To explore the pathways and patterns which CCAAT/enhancer binding protein β(CEBPβ) mRNA, miR-369-3p and rno-Rmdn2_0006 regulate the hepatocytes in G

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein ζ (CEBPO mRNA, miR-136-3p, rno-Crebrf_0009, rno-Slc38a9_0001, rno-LOCl00362999_0001 and rno- Got1_0001 regulate the hepatocytes in G

Objective Studies have shown that circular RNA (circRNA) is a molecular sponge of microRNA (miRNA) and can be used for the treatment and diagnosis of liver diseases. Therefore, this study aims to further investigate the expression profile of circRNA and its effect on autophagy in rat liver regeneration. Methods Based on the high-throughput sequencing in regenerated liver of 0 hour, 2, 6, 12, 24, 30, 36, 72, 120 and 168 hours after 2/3 hepatectomy in 60 rats, the expression profiles of circRNAs, miRNAs and mRNA were analyzed and their relationship were predicted by miRanda aug 2010 software. Furthermore, according to gene function → miRNA function → circRNA function, circRNAs and miRNAs that regulating autophagy were obtained in liver regeneration and compting endogenous (ceRNA) network was constructed. Results There were 102 circRNAs, 42 miRNAs and 153 mRNAs associated with autophagy involved in liver regeneration. Using bioinformatics analysis, 44 types of circRNAs, 13 types of miRNAs and 17 types of mRNA were found to interact with each other, and their co-expression network was constructed. Conclusion In this study, we screened out the circRNAs, miRNAs and mRNAs related to autophagy in liver regeneration and built the interaction network map.

Objective To investigate the regulation of liver regeneration (LR) by changes in energy metabolites in the initiation phase during rat liver regeneration. Methods Rats were randomly divided into 3 groups with 5 rats in each group, including two partial hepatectomy (PH) groups and one normal control group. Selective reaction monitoring/multiple reaction monitoring (SRM/MRM) was employed in the targeted metabolomics identification of 29 energy metabolites. Ingenuity Pathway Analysis (IPA) was applied for integration analysis, including canonical pathway and molecular interaction network. Results The levels of 3-phospho-D-glycerate, AMP, cyclic AMP, D-fructose 1, 6-bisphosphate, dihydroxyacetome phosphate (DHAP), guanosine monophosphate (GMP), guanosine triphosphate (GTP), nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinueleotide phosphate ( NADP ) significantly increased. The levels of alpha-ketoglutarate, beta-D-fructose 6-phosphate, cis-aconitate, D-glucose 6-phosphate, lactate, NADPH, oxaloacetate and pyruvate dramatically reduced. Through hierarchical clustering analysis of energy metabolisms, these energy metabolisms can be grouped into four clusters. IPA showed that the biomolecular changes in the priming phase of liver regeneration are mainly related to carbohydrate metabolism, cellular growth and proliferation, and organismal development. During the priming phase of liver regeneration, adenosine 5'-monphosphate-activated protein kinase (AMPK), hypoxia- inducible factor la (HIF-la), peroxisome proliferator-activated receptor (PPAR), protein kinase A (PKA) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways are involved in energy metabolism, and glycolysis may be the main mode of energy supply. Conclusion The result suggests that the changes of energy matabolites during the initial stage of LR play a regulatory role in live regeneration.