Effects of VEGF/VEGFR/K-ras signaling pathways on miRNA21 levels in hepatocellular carcinoma tissues in rats

• Published in: Genetics and molecular research 2015-01, Vol.14 (1), p.671-679
• Main Authors: Gao, J Z, Wang, Y L, Li, J, Wei, L X
• Format: Article
• Language: English
• Subjects: Animals; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Diethylnitrosamine - toxicity; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms - chemically induced; Liver Neoplasms - genetics; Liver Neoplasms - pathology; MicroRNAs - biosynthesis; MicroRNAs - genetics; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Proto-Oncogene Proteins p21(ras) - biosynthesis; Proto-Oncogene Proteins p21(ras) - genetics; Rats; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction - drug effects; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; Vascular Endothelial Growth Factor Receptor-2 - genetics
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/2015.January.30.10

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.