Establishment Of Protein-Protein Interaction Network Of Hepatocellular Carcinoma And The Study Of RNF43in Hepatocellular Carcinogenesis And Progress

Hepatocellular carcinoma(HCC) is a common cancer and ranks the third mortality in China. Traditional therapies are insufficient for HCC. As the development of HCC is a complicate process with multi-genes and multi-pathways, the only way to cure HCC is uncover the mechanisms of it.As microarray technique developing, it performs a more and more important role in cancer research area. At the same time, the development of database storing and sharing the large data from microarray promotes the progression of microarray. How to dig these data deeply to uncover the mechanism of HCC at genome level is a big challenge. In the first part of this study, we analyze a HCC microarray from Chen X using layered PPI network and attempted to uncover the mechanism of HCC.Based on the results of the first part, we analyze one of the expressed genes, RNF43. We use siRNA and shRNA technology to inhibit the expression of RNF43, and find whether knockdown of it could inhibit the malignant phenotype of HCC cells. Part I Meta-Analysis of HCC Microarray Data and Establishment of Layered PPI Network of HCC Specific ProteinsObjective:Hepatocellular carcinoma (HCC) generation is a complicate process with multi-genes and multi-pathways involved in,and its mechanism is far from understand. Our study now Meta-analyze the microarray data form Chen X and explore the expression difference of HCC specific genes, and analyze these genes with gene ontology to get the functional enrichment of specific biological processes. Finally, we established a PPI network of HCC specific genes to uncover the molecular mechanism in HCC development.Methods:We use the gene expression data from Chen X and compare with the HCC specific protein profiles from HPA to get the expression pattern of HCC specific genes. We filter the genes up-or down-regulated using SAM software. Using Cytoscape and its plug-ins Bionetbiulder, NetworkAnalyzer and Cereberal, we establish a PPI network of HCC specific genes and analyze these genes with gene ontology using David Gene ontology tools.Results:There are2617HCC specific genes in Chen's microarray data, including833upregulated,589downregulated,1169unchanged. After establish the PPI network of these genes,we layered the network according to the subcellular location of genes, we find that in the nucleus and cytoplasm region the upregulated genes are more than downregulated genes, but in the extracellular region and plasma membrane things are reverse. The upregulated genes mainly involved in nucleus transport, and down regulated genes mainly in carboxylic acid and amino acid metabolismConclusion:PPI network is a useful tool to explore the mechanism of HCC, and the expression pattern and function of genes is different according to the subcellular location. Part â…¡ The Study of a Novel Oncogene, RNF43in Hepatocellular Carcinoma.Objective:RNF43is a new found number of Ring finger proteins. It was found overexpression in colon cancer and was proved that could promote cell proliferation. Although RNF43was identified to be an oncogene in colon cancer, its role in HCC is largely unknown-Methods:Immunohistochemistry and qRT-PCR were used to detect the expression of RNF43in HCC tissues and cell lines. The correlation between RNF43overexpression and clinical pathological parameters was analyzed in98patients; siRNA and shRNA interference were used to knockdown RNF43, and study the effect of RNF43protein on proliferation, apoptosis, invasion and tumerigenesis ability of hepatocellular carcinoma cells. Microarray and JAK/STAT3, PI3K/AKT and MEK/ERK signaling analysis were performed to explore the mechanism of RNF43. Results:RNF43was commonly expressed in HCC tissues and cell lines, and this overexpression was correlated with positive vascular invasion, poor tumor differentiation and advanced tumor stage. Functional studies showed that knockdown of RNF43could induce apoptosis and inhibit proliferation, invasion, colony formation and xenograft growth of HCC cells. Microarray-based gene profiling demonstrated many genes involved in oncogenic processes such as cell proliferation, cell adhesion, cell motility, cell death, DNA repair and so on.Conclusion:These results suggest that RNF43acts as an oncogene in human hepatocellular carcinoma and antagonism of RNF43may be of interest for the treatment of HCC.