MicroRNA Interaction network in human: implications of clustered microRNA in biological pathways and genetic diseases
📝 Abstract
A novel group of small non-coding RNA, known as microRNA (miRNA) is predicted to regulate as high as 90% of the coding genes in human. The diversity and abundance of miRNA targets offer an enormous level of combinatorial possibilities and suggest that miRNAs and their targets form a complex regulatory network. In the present study, we analyzed 711 miRNAs and their 34, 525 predicted targets in the miRBase database which generate a complex bipartite network having numerous numbers of genes forming the hub. Genes at the hub (total 9877) are significantly over represented in genes with specific molecular functions, biological processes and biological pathways as revealed from the analysis using PANTHER. We further construct a miRNA co-target network by linking every pair of miRNAs which co-target at least one gene. The weight of the link, which is taken to be the number of co-targets of the pair of miRNAs vary widely, and we could erase several links while keeping the relevant features of the network intact. The largest connected sub-graph, thus obtained, contains 479 miRNAs. More than 75% of the miRNAs deregulated in 15 different diseases collected from published data are found to be in this largest sub graph. We further analyze this sub-graph to obtain 70 small clusters containing total 330 miRNAs of 479. We identified the biological pathways where the co-targeted genes in the clusters are significantly over- represented in comparison to that obtained with that are not co-targeted by the miRNAs in the cluster. Using published data, we identified that specific clusters of miRNAs are associated with specific diseases by altering particular pathways. We propose that instead of single miRNA, clusters of miRNA that co-targets the genes are important for the regulation of miRNA in diseases.
💡 Analysis
A novel group of small non-coding RNA, known as microRNA (miRNA) is predicted to regulate as high as 90% of the coding genes in human. The diversity and abundance of miRNA targets offer an enormous level of combinatorial possibilities and suggest that miRNAs and their targets form a complex regulatory network. In the present study, we analyzed 711 miRNAs and their 34, 525 predicted targets in the miRBase database which generate a complex bipartite network having numerous numbers of genes forming the hub. Genes at the hub (total 9877) are significantly over represented in genes with specific molecular functions, biological processes and biological pathways as revealed from the analysis using PANTHER. We further construct a miRNA co-target network by linking every pair of miRNAs which co-target at least one gene. The weight of the link, which is taken to be the number of co-targets of the pair of miRNAs vary widely, and we could erase several links while keeping the relevant features of the network intact. The largest connected sub-graph, thus obtained, contains 479 miRNAs. More than 75% of the miRNAs deregulated in 15 different diseases collected from published data are found to be in this largest sub graph. We further analyze this sub-graph to obtain 70 small clusters containing total 330 miRNAs of 479. We identified the biological pathways where the co-targeted genes in the clusters are significantly over- represented in comparison to that obtained with that are not co-targeted by the miRNAs in the cluster. Using published data, we identified that specific clusters of miRNAs are associated with specific diseases by altering particular pathways. We propose that instead of single miRNA, clusters of miRNA that co-targets the genes are important for the regulation of miRNA in diseases.
📄 Content
arXiv:0901.4211v1 [q-bio.GN] 27 Jan 2009 MicroRNA Interaction network in human: implications of clustered microRNA in biological pathways and genetic diseases Sushmita Mookherjee1, Mithun Sinha2, Saikat Mukhopadhyay3, Nitai P. Bhattacharyya2,3,∗and P. K. Mohanty4† 1Centre for Applied Mathematics and Computational Science, 2Structural Genomics Section, 3Crystallography and Molecular Biology Division, 4Theoretical Condensed Matter Physics Division, Saha Institute of Nuclear Physics,1/AF Bidhan Nagar, Kolkata, 700064 India. (Dated: November 3, 2018) A novel group of small non-coding RNA, known as microRNA (miRNA) is predicted to regulate as high as 90% of the coding genes in human. The diversity and abundance of miRNA targets offer an enormous level of combinatorial possibilities and suggest that miRNAs and their targets form a complex regulatory network. In the present study, we analyzed 711 miRNAs and their 34, 525 predicted targets in the miRBase database (http://microrna.sanger.ac.uk/ , version 10), which gen- erate a complex bipartite network having numerous numbers of genes forming the hub. Genes at the hub (total 9877) are significantly over represented in genes with specific molecular func- tions, biological processes and biological pathways as revealed from the analysis using PANTHER (http://www.pantherdb.org/genes/) . We further construct a miRNA co-target network by linking every pair of miRNAs which co-target at least one gene. The weight of the link, which is taken to be the number of co-targets of the pair of miRNAs vary widely, and we could erase several links while keeping the relevant features of the network intact. The largest connected sub-graph, thus obtained, contains 479 miRNAs. More than 75% of the miRNAs deregulated in 15 different diseases collected from published data are found to be in this largest sub graph. We further analyze this sub-graph to obtain 70 small clusters containing total 330 miRNAs of 479. We identified the biological pathways where the co-targeted genes in the clusters are significantly over- represented in comparison to that obtained with that are not co-targeted by the miRNAs in the cluster. Using published data, we identified that specific clusters of miRNAs are associated with specific diseases by altering particular pathways. We propose that instead of single miRNA, clusters of miRNA that co-targets the genes are important for the regulation of miRNA in diseases. I. INTRODUCTION Micro-RNA (miRNA) belongs to a class of small non-coding single stranded RNA, approximately 21 nu- cleotides long, which negatively regulate gene expres- sions. Mature miRNA interacts with the 3′ untrans- lated regions (3′ UTR) of the gene in human and down regulate the expression of the target either by degrad- ing the mRNA or inhibiting the translation. In some cases, increased expressions of the target gene by miR- NAs have also been reported (reviewed in [1]). Recent experiments show, at least in few specific cases, that the mature miRNA can alters the expressions of the genes by binding to the coding regions as well as 5′ UTR of genes [2-4] providing further complex regulation of the genes by miRNAs. It has been proposed on the basis of theoretical analysis that as many as 30% of genes in the human genome may be the target of miRNA [5]. Re- cent, estimates predict that as large as 90% human genes are targets of miRNA [6]. However, experimental vali- dation of such prediction is largely lacking. Function of each region of the mature miRNA is not well defined, al- though, the seed region (2nd to 7th position from the 5′ end of the mature miRNA), is the most important region ∗E-mail address: nitaipada.bhattacharya@saha.ac.in †E-mail address: pk.mohanty@saha.ac.in that interacts with 3′ UTR for regulation of the target genes. The other regions known as extended seed and delta seed regions also contribute to the target selection [7]. The diversity and abundance of miRNA targets of- fer an enormous level of combinatorial possibilities and suggest that miRNAs and their targets appear to form a complex regulatory network. Functions of miRNA is known only for some, although deregulation of miRNAs has been shown in number of diseases like various types of cancers [8, reviewed in 9] cardiovascular development and heart failure [10]. In- volvement of miRNAs in various diseases has been re- cently reviewed [11]. Studies of various diseases and nor- mal cellular processes indicate that miRNAs are involved in immune-system [12]; stem cell renewal and develop- ment [13, 14]. Using inhibitors of different miRNAs it has also been shown that several miRNAs are involved in cell death, cell growth and proliferation [15]. The ex- tent of modulation of the targets and their influences on the biological processes that lead to alteration of cellular phenotype varies considerably [16]. In a recent study in Caenorhabiditis elegans (C. elegans) where 83% of the C. elegans miRNA (total 95 miRNA) are mutated and effects of th
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