Study On MiRNA Regulation Mechanism In Cancer Based On Expression Pattern Analysis

microRNAs (miRNAs) are a class of short (18~25nt) non-coding RNAs which cancontrol the expression level of their target mRNAs. One miRNA can be base-pairing (orincompletely base-pairing) with some protein-coding genes processed from mRNAs, andinhibits the expression of these mRNAs. We think that miRNAs cannot be translated butthey can regulate other genes expression. The expression level of miRNA and its targetmRNAs are positively related.Introns form the majority of non-coding sequences in protein-coding DNAs.Pre-mRNAs transcripted from protein-coding DNAs can be divided into four parts:5’non-coding region, exon, intron and3’non-coding region. Broadly speaking, we can alsotake5’ and3’ non-coding regions as introns in a very different form. Initially, these intronswere considered as useless regions in the sequences, the misunderstanding was changeduntil intronic miRNAs were found. At the present time, there are408intronic miRNAswhich accounting for nearly a quarter of known miRNAs. It can be assumed that theexpression level of intronic miRNAs released from generalized introns and their hostmRNAs are negatively related.According to the above two regulatory relations, we can build the regulatory networkof “Host mRNA—intronic miRNA—Target mRNA” by analyzing the paired microarraydata of miRNA and mRNA. On the base of above theories, we use the published seriesGSE16441，which contains miRNA and mRNA expression data of17samples of renal cellarcinoma and17samples from their adjacent normal tissue from GEO (Gene ExpressionOmnibus) database, to analyze the unusual co-transcriptional relationship between intronicmiRNA and its host mRNA, and unusual inhibitive effects between intronic miRNA and itstarget mRNAs. Then we try to discover the interaction mechanism between host mRNA andother mRNA by intronic miRNA in renal cell carcinoma. At last, we got18abnormal casesof host mRNAs and their released intronic miRNAs relations,29abnormal intronicmiRNAs inhibit their target mRNAs relations in renal cell carcinoma.Over the past decade, many studies about miRNAs inhibiting their target mRNAs incancers are processed, but no regulating relations between host mRNA and their intronicmiRNAs are researched. In this article, we can find that intronic miRNAs released fromintrons and other non-coding RNA sequence provide regulation of gene expression onanother level, which form a complex fine-tuning network of gene expression. This complexnetwork contains a simple triple “host miRNA—intronic miRNA—target mRNA”. Due to the amount of gene expression are signaled by the amount of mRNA expression in geneexpression profile, we keep the gene and its transcription mRNA as the same element.Merge the overlapping mRNAs and miRNAs in all the triples, we will build a morecomplex miRNA—mRNA regulatory network. As a summary, we can establish two kindsof abnormal regulatory relations:1, abnormal host mRNAs and their released intronicmiRNAs.2, abnormal intronic miRNAs and their target mRNAs.This experiment can be divided into5parts:1, do difference expression analysis andclustering analysis.2, screen abnormal intronic miRNAs whose expression are abnormal,and establish the relationships that intronic miRNAs inhibit their target mRNAs.3, buildlocal database and local Blast.4, design scoring function and screen the local Blast resultsand obtain the co-expression relationships between host mRNAs and their released intronicmiRNAs.5, build the miRNA regulatory network in cancers by integration of the abovetwo kinds of relationships.By analyzing the miRNA regulatory network in the cancer, we can find many biologyphenomenon which have been proved. This prove that our miRNA regulatory network havebiological significance. During the experiment，many inhibiting relationships between highexpression miRNAs and their target mRNAs but less low expression miRNAs reducing theinhibiting level of their target mRNAs were found in renall cell carcinoma. Examine if thisis a pattern that most abnormal expression miRNA regulate the expression of mRNAs incancer (in fact, the author has analysed the microarray data of melanoma, non small celllung cancer, pancreatic cancer, liver cancer and lymphoma, the trend is common). There isanother possibility that we pay little attention on the low expression miRNAs in diseases,and more biological experiments might be needed.After the rationality of the experiment are verified, we continue develop thisexperiment to an on line miRNA regulatory network analysis server. In this server, userscan upload miRNA and mRNA expression data files and compute the miRNA regulatorynetwork. The server will return the result to the users and give rationally suggests tobiologists who study the pathogenesis of cancers. In this server, users can also share theirresults with others which promote the research of cancers. For the convenience of users, wealso provide difference expression analysis and gene enrichment analysis. We have a WebService which make users do batch computing. You can download a java client from ourwebsite or develop a client by your own languages by the WSDL file published.