Abstract

Increasing amounts of evidence indicate that noncoding RNAs (ncRNAs) have important roles in various biological processes. Here, miRNA, lncRNA, and mRNA expression profiles were analyzed in human HepG2 and L02 cells using high-throughput technologies. An integrative method was developed to identify possible functional relationships between different RNA molecules. The dominant deregulated miRNAs were prone to be downregulated in tumor cells, and the most abnormal mRNAs and lncRNAs were always upregulated. However, the genome-wide analysis of differentially expressed RNA species did not show significant bias between up- and downregulated populations. miRNA-mRNA interaction was performed based on their regulatory relationships, and miRNA-lncRNA and mRNA-lncRNA interactions were thoroughly surveyed and identified based on their locational distributions and sequence correlations. Aberrantly expressed miRNAs were further analyzed based on their multiple isomiRs. IsomiR repertoires and expression patterns were varied across miRNA loci. Several specific miRNA loci showed differences between tumor and normal cells, especially with respect to abnormally expressed miRNA species. These findings suggest that isomiR repertoires and expression patterns might contribute to tumorigenesis through different biological roles. Systematic and integrative analysis of different RNA molecules with potential cross-talk may make great contributions to the unveiling of the complex mechanisms underlying tumorigenesis.

Highlights

  • Large-scale, genome-wide analyses have indicated that much of the human genome is transcribed, yielding a great many nonexonic transcripts [1, 2]

  • These small, single-stranded RNAs negatively regulate gene expression through partial base-pairing with target messenger RNAs

  • The raw small RNA sequencing data can be available in the Sequence Read Archive (SRA) database, and the messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) microarray data can be available in the European Molecular Biology L aboratory-Euro-pean Bioinformatics Institute (EMBL-EBI) database

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Summary

Introduction

Large-scale, genome-wide analyses have indicated that much of the human genome is transcribed, yielding a great many nonexonic transcripts [1, 2]. BioMed Research International to regulate gene expression through various mechanisms, such as complementary binding to protein-coding transcripts in the form of cis-antisense lncRNAs [16,17,18,19,20]. The many biological roles of ncRNAs have drawn a great deal of concern, systematic and integrative analyses of many kinds of RNA molecules (including functional mRNAs) have been rare. We ever performed analyses of miRNA-mRNA and miRNAmiRNA interactions using miRNA and mRNA expression profiles [26], but it is not enough to further understand the potential relationships between different RNA molecules, especially involving the novel concerned lncRNAs. In the present study, the close relationships between ncRNAs and mRNAs were examined through simultaneously profiling of miRNA, lncRNA, and mRNA in HepG2 and L02 cells using high-throughput technologies. The results of the present study will enrich the genome-wide analysis of different molecules with potential cross-talk and contribute to further systematic studies of tumorigenesis

Materials and Methods
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