Research Based On Several MiRNA Regulatory Network Of Breast Cancer

The successful completion of the Human Genome Project (HGP) makes it possible for human to research themselves genetically by analyzing massive data, which obtained from the HGP. Moreover, construction of gene expression regulation network enables people to explore the organisms function from the molecular level.The elements of gene regulatory network (GRN) in living cells usually include proteins, nucleic acids, or microRNA (miRNA), etc. However, changes in the GRN structure are underlying causes for certain physiological phenomena, such as tumorigenesis and tumor deterioration. Breast cancer (BC), which is one of the major malignant tumors, is a serious threat to women’s health with noticeably increased mortality. BC starts as a local disease, but it can metastasize to the other organs. Metastatic BC is the major difficult factor for treatment of advanced breast cancer. It suggests that early diagnosis for patients is of vital importance. Recent studies proved the involvement of miRNA in BC metastases. It was found that miRNA contribute to oncogenesis by functioning as down-regulated tumor suppressors, and also can function as over-expressed oncogenes. For another, there has an increased focus on p53gene since its function of resist cancer has been discovered. The p53gene is the core of p53network, and it is also the first to be confirmed as a tumor suppressor gene, which regulates the major life course events, such as cell division cycle and DNA replication. Cells immortality occurs once the tumor suppressor gene becomes dysfunctional, and resulted in the tumor formation eventually. This paper focused on the tumor-associated gene regulatory networks and the work in following aspects has been done:First, this paper introduced tumor systems biology as well as the biology background of miRNA, and then reviewed four methods in which GRN can be studied. Each of these modules presents advantages and disadvantages. Finally the research status and significance of tumor gene regulatory network were summarized.Second, research on breast cancer metastasis related miRNA network based on a Boolean network. Firstly integrated the miRNA information involved in the BC metastasis through collecting literatures, the results was divided into two groups: oncogenic miRNA, which are up-regulated in BC metastasis, denoted by1; on the contrary, tumor suppressor miRNA are down-regulated and denoted by0. And then constructed a comprehensive BC metastasis related miRNA regulatory network. The analysis results based on a Boolean network shows that it has great biological significances and provides new perspective for the later research.Third, the paper researched relationship between miRNA and p53network. To illustrate the p53regulatory pathway visually, this study analyzed main frame of the relationship between miR-34family and p53regulatory network by simplifying the existing complex p53network. The results show that there is accurate regulation between p53gene and miR-34family members.The method used in this study is not completely reliable on a biological level for followings:the analysis of miRNA mediated BC metastasis regulatory network based on Boolean network, which emphasize a global network rather than a quantitative biochemical model compared to the real gene networks. Actually, it regard the within genetic functions and interactions as logic rules. However, using logical inference rules of each gene often leads errors because of the complexity of interactions between genes. Moreover, in practice, relationship between miRNA and p53regulatory network is too complex to simulate by using such a simplified model which only contained key molecules. We need further research.