ABSTRACT
The aim of this study was to investigate the effects of the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)/K-ras signaling pathways on miRNA21 levels in hepatocellular carcinoma tissues in rats. Eighteen male Sprague-Dawley rats were randomly divided into normal control, model, and VEGF blocking agent groups (N = 6/group). The expression of VEGF mRNA, K-ras protein, and miRNA21 increased significantly (P < 0.05) in the model group compared with the normal control group, and decreased dramatically in the VEGF blocking agent group compared to the model group. The expression of VEGFR mRNA in the model group was higher than that of the control group, and the expression of VEGFR mRNA in the VEGF blocking agent group was significantly higher than that of the control group (P < 0.05). Statistically, there was no difference between the expression of VEGFR mRNA for the VEGF blocking agent group and the model group (P > 0.05). Finally, the expression of the miRNA21 gene in the VEGF blocking agent group was higher than in the control group, and there was a significant statistical difference noted; Pearson's correlation analysis demonstrated that the expression of K-ras protein was positively correlated with miRNA21 in the experimental groups (P = 0.001). The above results showed that the VEGF/VEGFR/K-ras signaling pathway might promote the occurrence and development of hepatocellular carcinoma cells through regulating expression of miRNA21, which has potential clinical value for the development of therapies against biological targets and determining prognosis for patients with hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , MicroRNAs/biosynthesis , Proto-Oncogene Proteins p21(ras)/biosynthesis , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor Receptor-2/biosynthesis , Animals , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/pathology , Diethylnitrosamine/toxicity , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/chemically induced , Liver Neoplasms/pathology , MicroRNAs/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Proto-Oncogene Proteins p21(ras)/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
To investigate the effect of the HMG-CoA reductase inhibitor lovastatin on the expression of the receptor for hepatic low-density lipoprotein (LDL) in a rat model with kidney disease, and to identify the mechanisms in statin treatment of nephrotic syndrome with hyperlipidemia, a rat model with nephrotic syndrome was established. Thirty male Sprague-Dawley rats were treated with lovastatin for 2 weeks using gavage. The expression of protein and mRNA of the LDL receptor in the rat liver was detected with Western blot and RT-PCR, respectively, and blood-biochemical indices were also recorded for each group. Compared with the untreated control group, lovastatin treatment significantly decreased the levels of serum total cholesterol, LDL cholesterol, triglycerides, and urinary protein. In addition, lovastatin treatment significantly increased the levels of serum albumin and hepatic LDL receptor proteins, but had no effect on the expression of hepatic LDL receptor mRNA. Treatment with lovastatin markedly increased the expression of the hepatic LDL receptor in rats with nephrotic syndrome, which was accompanied by significantly improved hyperlipidemia.
Subject(s)
Anticholesteremic Agents/administration & dosage , Hyperlipidemias/drug therapy , Lovastatin/administration & dosage , Nephrotic Syndrome/drug therapy , Receptors, LDL/genetics , Receptors, LDL/metabolism , Animals , Anticholesteremic Agents/therapeutic use , Cholesterol, LDL/blood , Disease Models, Animal , Hyperlipidemias/complications , Liver/drug effects , Liver/metabolism , Liver/pathology , Lovastatin/therapeutic use , Male , Nephrotic Syndrome/pathology , Rats , Rats, Sprague-Dawley , Triglycerides/bloodABSTRACT
Milk composition and body measurement traits, influenced by genes and environmental factors, play important roles in value assessments of efficiency and productivity in dairy goats. Lactoferrin (LF), involved in the efficient expression of protein in milk, is also an anabolic factor in skeletal tissue and a potent osteoblast survival factor. Therefore, it is an important candidate gene for milk composition and body measurement trait selection in marker-assisted selection. We employed PCR-SSCP and DNA sequencing to screen the genetic variations of the LF gene in 549 Chinese dairy goats. A novel single-nucleotide polymorphism (SNP) (G198A in exon II) of the LF gene was detected. The frequencies of the AA genotype were 0.0285 and 0.0261 in GZ and SN populations, respectively. Both populations were found to have low levels of polymorphism and were in Hardy-Weinberg disequilibrium (P < 0.05). We found significant (P < 0.05) associations of the SNP marker with milk protein and acidity in the total population; animals with the AA genotype had higher mean values for milk protein than those with the GA genotype. Animals with genotype AA had higher mean values for withers height than those with genotype GG (P < 0.05). We concluded that this SNP of the LF gene has potential as a genetic marker for milk composition and body traits in dairy goat breeding.