RESUMO
Regenerating islet-derived protein (Reg) could participate in the occurrence of diabetes mellitus, inflammation, tumors, and other diseased or damaged tissues. However, the correlation of Reg with acute hepatic failure (AHF) and hepatocellular carcinoma (HCC) is poorly defined. To reveal the expression profiles of Reg family and their possible regulatory roles in AHF and HCC, rat models of HCC and AHF were separately established, and Rat Genome 230 2.0 was used to detect expression profiles of Reg-mediated signaling pathways-associated genes from liver tissues in AHF and HCC. The results showed that a total of 79 genes were significantly changed. Among these genes, 67 genes were the AHF-specific genes, 45 genes were the HCC-specific genes, and 33 genes were the common genes. Then, K-means clustering classified these genes into 4 clusters based on the gene expression similarity, and DAVID analysis showed that the above altered genes were mainly associated with stress response, inflammatory response, and cell cycle regulation. Thereafter, IPA software was used to analyze potential effects of these genes, and the predicted results suggested that the Reg-mediated JAK/STAT, NF-κB, MAPK (ERK1/2, P38 and JNK), PLC, and PI3K/AKT signaling pathways may account for the activated inflammation and cell proliferation, and the attenuated apoptosis and cell death during the occurrence of AHF and HCC.
Assuntos
Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Litostatina/metabolismo , Falência Hepática Aguda/genética , Neoplasias Hepáticas/genética , Transdução de Sinais/genética , Animais , Carcinoma Hepatocelular/patologia , Ciclo Celular/genética , Modelos Animais de Doenças , Humanos , Inflamação/genética , Fígado/patologia , Falência Hepática Aguda/patologia , Neoplasias Hepáticas/patologia , Masculino , Família Multigênica , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Fisiológico/genéticaRESUMO
Cell proliferation constitutes the fundamental process and driving force behind regrowth during liver regeneration (LR). However, it remains unclear how competing endogenous RNA (ceRNA) networks affect hepatocyte proliferation and liver regeneration. Therefore, this study was designed to explore an LR-specific ceRNA network, which regulates cell proliferation. Based on the microarray data of mRNAs, and high-throughput sequencing data of miRNAs and circRNAs from regenerating livers, this study initially applied known 1484 LR associated mRNAs to perform GO analysis, and then selected 169 LR associated mRNAs involved in cell proliferation and the cell cycle. Subsequently, 188 interactive miRNA-mRNA pairs and 5206 circRNA-miRNA pairs, respectively, were predicted using bioinformatics methods. Next, in view of the differential expressions of these ceRNAs during LR, 26 miRNA-mRNA pairs and 71 circRNA-miRNA pairs were applied to generate a circRNA-miRNA-mRNA regulatory network, and only 14 triple interactive groups were obtained based on the predicted inverse interactions among ceRNAs. Finally, circ_19698/miR-423-5p axis was demonstrated to promote cell proliferation by modulating the expression of MYC, CCNA2, and CCND1 in rat BRL-3A cells. This study suggests a potential regulatory mechanism of cell proliferation in regenerating livers, as well as a novel pathway for modulating ceRNA networks to promote liver regeneration.
Assuntos
Biologia Computacional , Redes Reguladoras de Genes , Regeneração Hepática/genética , MicroRNAs/genética , RNA Circular/genética , Animais , Ciclo Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
Aim: This study aimed to examine the effects of osteopontin (OPN) on hepatocyte growth and liver regeneration (LR). Methods: A recombinant lentivirus expressing OPN and OPN-siRNAs were used to treat BRL-3A cells, while the adenovirus expressing OPN or OPN-targeted shRNA were applied for rat primary hepatocytes. Moreover, rrOPN and OPN-Ab were added to treat BRL-3A. Next, rrOPN was administrated into rat regenerating livers. Then in vitro and in vivo assays were performed to evaluate the biological function of OPN in hepatocyte growth and LR. Results: OPN overexpression facilitated proliferation and viability of BRL-3A cells and primary hepatocytes, while OPN silencing reversed these effects. Similarly, rrOPN stimulated cell cycle progression and viability, but OPN-Ab led to cell cycle arrest and decreased viability. OPN overexpression induced the expression of p-STAT3, p-AKT and CCND1, and OPN siRNA led to reduction of p-AKT and CCND1. Furthermore, rrOPN promoted the expression of p-STAT3 and p-AKT, while OPN-Ab and PI3K/Akt inhibitor LY294002 both inhibited the expressions of p-AKT and Bcl2. Moreover, LR rate, serum IL-6 and TNF-α, Ki-67+ proportion and the phosphorylation of STAT3, AKT and p65 were augmented by rrOPN treatment. Conclusion: OPN promotes hepatocyte proliferation both in vitro and in vivo through STAT3 and AKT signaling pathways.
Assuntos
Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Osteopontina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Hepatócitos/metabolismo , Regeneração Hepática/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Graphene consists of two-dimensional sp2-bonded carbon sheets, a single or a few layers thick, which has attracted considerable interest in recent years due to its good conductivity and biocompatibility. Three-dimensional graphene foam (3DG) has been demonstrated to be a robust scaffold for culturing neural stem cells (NSCs) in vitro that not only supports NSCs growth, but also maintains cells in a more active proliferative state than 2D graphene films and ordinary glass. In addition, 3DG can enhance NSCs differentiation into astrocytes and especially neurons. However, the underlying mechanisms behind 3DG's effects are still poorly understood. Metabolism is the fundamental characteristic of life and provides substances for building and powering the cell. Metabolic activity is tightly tied with the proliferation, differentiation, and self-renewal of stem cells. This study focused on the metabolic reconfiguration of stem cells induced by culturing on 3DG. This study established the correlation between metabolic reconfiguration metabolomics with NSCs cell proliferation rate on different scaffold. Several metabolic processes have been uncovered in association with the proliferation change of NSCs. Especially, culturing on 3DG triggered pathways that increased amino acid incorporation and enhanced glucose metabolism. These data suggested a potential association between graphene and pathways involved in Parkinson's disease. Our work provides a very useful starting point for further studies of NSC fate determination on 3DG.
RESUMO
BACKGROUND: Accumulating data have reported that GSTM1 polymorphism may be related to nasopharyngeal cancer (NPC) and laryngeal cancer (LC). This meta-analysis was performed to investigate the relationship between GSTM1 polymorphism and risks of NPC and LC. METHODS: Pubmed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for potential articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship of GSTM1 polymorphism with the risks of NPC and LC. I2>50% or P<0.05 indicates significant heterogeneity. When heterogeneity existed, the random-effects model was used to pool data, otherwise, the fixed-effects model was adopted. Publication bias was detected by Begg's funnel plot and Egger's regression. Quality of each study was evaluated by Newcastle-Ottawa Scale. RESULTS: Thirty-two eligible articles were included. Pooled outcome suggested the significant relationship of GSTM1 null genotype with increased risk of LC (OR =1.28, 95% CI =1.05-1.54). Compared with hospital-based (HB) population, GSTM1 null genotype was also related to increased risk of LC (OR =1.38, 95% CI =1.06-1.80). Positive relationship of GSTM1 null genotype with enhanced risk of NPC was observed (OR =1.43, 95% CI =1.26-1.63). A similar trend was also observed in the subgroup analysis by source of control (population-based [PB]: OR =1.39, 95% CI =1.18-1.63; HB: OR =1.52, 95% CI =1.22-1.89). CONCLUSION: GSTM1 null genotype is related to increased risk of NPC and LC.
RESUMO
PURPOSE: The purpose of this study is to investigate the associations of the x-ray repair cross-complementing 1 gene (XRCC1) single nucleotide polymorphisms (SNPs) Arg194Trp, Arg280His, and Arg399Gln with gastric cancer risk. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, CINAHL, International Bibliography of the Social Sciences, and Social Sciences Citation Index were searched. Two authors independently searched for relevant studies in any language from 1966 to Jan 2013. RESULTS: Seventeen studies with a total population of 10427 participants were identified. The results showed there were no associations of Arg399Gln polymorphism with gastric cancer, no matter in the co-dominant model, dominant model or recessive model. For Arg194Trp and Arg280His polymorphism, still no significant differences were found between control groups and GC groups in samples regardless of race. However, significant associations between Arg194Trp polymorphism and gastric cancer were found in Asian. The Asia with mutant genotype (Trp/Trp+Arg/Trp) had a higher risk of GC compared with the Asian with wild genotype (Arg/Arg). CONCLUSION: Our meta-analysis indicates that genetic polymorphism of the XRCC1 Arg399Gln and Arg280His do not have an association with gastric cancer risk. However, for Arg194Trp polymorphism, mutant gene carriers had a higher GC risk in Asian.
Assuntos
Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Gástricas/genética , Povo Asiático , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
In the current study, a proportion of lung adenocarcinoma was shown to reduce GPC5 expression in the absence of transcriptional silencing of the tumor suppressor gene, GPC5, by aberrant methylation of CpG islands. It was hypothesized that the loss of GPC5 expression is associated with upregulation of miR620 in human lung adenocarcinoma tissue compared with the matched normal lung tissue. The downregulation of GPC5 in lung adenocarcinoma cell lines is regulated by miR620 through binding of the 3'untranslated region. Furthermore, blockage of miR620 inhibited the proliferation, migration and invasion of lung adenocarcinoma cells by directly regulating GPC5, and GPC5 knockdown eliminates this phenotype. These results provided a novel insight into the mechanism of miRNA regulation in lung adenocarcinoma.
Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Glipicanas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Supressoras de Tumor/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Movimento Celular/genética , Proliferação de Células , Metilação de DNA , Regulação para Baixo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Interferência de RNA , Transcrição GênicaRESUMO
BACKGROUND: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. RESULTS: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down- regulate the expression of MMP-3, Twist and Snail. CONCLUSIONS: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes.