Bioinformatics And Evolutionary Analysis Of MicroRNAs

microRNAs (miRNAs) are endogenously expressed small noncoding RNAs with transcripts ranging between 18-23 nt in length, they can regulate the expression of protein-coding genes through translational inhibition or processing mRNAs by base pairing to mRNAs 3'-untranslated regions (3'-UTRs). As an important kind of gene expression regulator, profound influences of miRNAs on diverse regulatory pathways, such as embryo development, cell division, differentiation, apoptosis, hematopoiesis and cancer development, are widely recognized. At this time, more than one thousand miRNA genes have been identified in the human genome. The properties, expression mechanism, evolution miRNAs have turned into the hotspots of molecular biology and bioinformatics. In this analysis, we mainly concentrate on the cancer related miRNAs, expression regulation mode of the target genes, intronic miRNAs and evolution of specific miRNA family, carried out some initial research by bioinformatic and statistical tools.Recently, more and more evidence suggests that aberrant expression of miRNAs may contribute to many types of human diseases, including cancer. miRNAs can be a novel kind of biomarker for the digonesis and treatment. For integrate the expression information about cancer related miRNAs, we first searched for the miRNA expression profiles in various kinds of human cancers in the Gene Expression Omnibus (GEO) database, and then used the method of Significance Analysis of Microarrays to screen the differentially expressed miRNAs in human cancers. Totally 607 cancer related miRNAs were finally identified. We also designed and constructed a database, called the dbDEMC, a database of differentially expressed miRNAs, to explore aberrantly expressed miRNAs among different cancers. This database is expected to be a valuable source for identification of cancer-related miRNAs, thereby helping with the improvement of classification, diagnosis and treatment of human cancers.The expression mode of miRNAs on target genes turned out to be another hotspot of bioinformatics. It is suggests that there are two different kind of gene expression mode of microRNAs:adjust the average expression level and/or reduce the fluctuation of target genes. We first screened out more than one hundred expression profiles based on the HGU133 plus2.0 microarray platform in the GEO database, and then filtered out different group of genes that have different expression mode, including the steady expressed genes and fluctuate genes, the preferential regulation of miRNA regulation on these genes was analyzed. We found that miRNAs preferentially regulate the steady expressed genes, which suggests they can enhance the stability of the expression of target genes. Further more, we found opposite effect between transcription factors and miRNAs. This analysis provide novel clue for understanding the mechanism of gene expression regulation.Most miRNAs genes locate in the intergenetic region, whereas some of them locate in the intronic region of protein coding genes. Their transcription may depend on the transcriptional elements of the host genes. Here we also analyzed the characteristics of the host gene of miRNAs. We found that the lengths of host genes are larger than the non-host genes, this is due to the increased number of their introns and exons. The phylogenetic distribution analysis of the intronic miRNAs among various species demonstrated that intronic miRNAs genes mainly emerged at three different time point, including the origin of vertebrate, eutheria and primate.At last, we use a vertebrate specific miRNA family, the miR-181 as an example, to analysis the origin and evolution of miRNA gene families in vertebrate genomes. There is only one copy of the miR-181 family was found in the urochordata genome, whereas there are six copies of this family in the vertebrate genome. We found that it is the whole genome duplication for twice and tandem duplication between them that form this family in the vertebrate genome. The functional analysis of the target genes of this family demonstrates that they mainly involved in the expression regulation, inter-cellular signaling, cell growth, division and proliferation.