| A miRNA is a class of non-coding small RNA molecule and in general composed of 22 nucleotides.Increasing studies demonstrated that the miRNAs not only play a key regulatory role in many biological processes,but also is associated with disease development especially cancer.Protein-protein interaction(PPI)network is essential to almost every process in a cell,so the dysfunction of PPI network can result in the development of disease.In addition,by mediating the proteins in PPI network,miRNAs can perform a more general and specific regulatory effects in many biological process.As a result,it is necessary to study the role that miRNAs play in the disease development based on the analysis of PPI network.But it remains unclear about the mechanism by which miRNAs regulate PPI network,particularly in the state of disease.This study is performed to analyze the sequence similarity of miRNAs associated with cancer and understand their regulatory effects on the targeting proteins.It consisted of three parts,as follow:Part ?: The miRNAs specifically associated with six kinds of cancer,including breast cancer,esophagus cancer,lymph cancer,renal carcinoma,prostatic carcinoma and glioma,were collected and the sequence similarity among them was analyzed using the sequence alignment.Based on the analysis of sequence similarity,we can indirectly evaluate the similarity among their targets and basically understand the regulatory effects on targets mediated by those miRNAs.Part ?: A human PPI network was built based on the experimentally confirmed PPI data from five major PPI databases.Furthermore,the regulatory relation between miRNAs and proteins was obtained from miRbase database and prediction of miRanda.Taking these results together,we can analyze the relation between network topologies and regulation of miRNAs.Part ?: A network specifically associated with Hodgkin's lymphoma(HL)was developed and this network contained the regulatory relation between miRNAs and proteins as well as PPI.On the basis of analysis of such network,we can conclude the regulatory patterns of miRNAs towards this HL-specific network and identify the key proteins and miRNAs to HL.The results obtained from above three researches are listed below,respectively.Firstly,based on the expression profile of miRNAs in cancer cells compared to normal cells,the collected miRNAs were divided into two groups,in which miRNAs were up and down expressed,respectively.Sequence similarity was calculated for two groups of miRNAs according to the type of cancer.The results show that there are no significant similarity among miRNAs associated with both one and several cancers.It indicates that these miRNAs with similar functions don't regulate the common targets,rather than the PPI network.Secondly,the features of proteins regulated by miRNAs in PPI network were characterized based on the human PPI network and miRNA target predictions.The results show that there are few proteins that can be mediated by multi miRNAs and few miRNAs that can regulate many proteins simultaneously.The results imply that the analysis of miRNA regulation should be performed from the network perspective,combining with the PPI network.Thirdly,we constructed a HL-specific PPI network based on the experimentally validated PPI data.Such HL-specific network can be further divided into 5 sub-networks and 49 proteins are identified as the backbone of HL-specific network making up and connecting these 5 sub-networks.Moreover,we explored the miRNA regulation on HL-specific PPI network and subsequently constructed a simplified PPI network combined with the regulation of miRNAs on proteins to better understand the relation between HL-related proteins and miRNAs.Based on the analysis of such complicated network,we proposed three kinds of simple regulation patterns.According to the regulation of miRNA on PPI network,we identified 5 core miRNAs that can mediate about 90% proteins in PPI network as the potential biomarkers for diagnostic of HL. |
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