Abstract
ncRNAs have been identified as potential regulatory molecules and have multiple biological roles. Aberrant expression of specific ncRNAs contributes to multiple biological processes and many human diseases. Herein, we simultaneously profiled miRNA, lncRNA and mRNA in human HepG2 and L02 cells applying high-throughput sequencing and micro-array technologies. Abnormal miRNA, lncRNA and mRNA profiles were assessed through fold change filtering. A cross-platform integrated analysis method was developed to analyze differentially expressed miRNA, lncRNA and mRNA profiles. miRNA-mRNA interaction was analyzed according to their functional relationships. Target mRNAs of aberrantly expressed miRNAs were obtained from experimentally validated datasets or predicted using some programs. Generally, multiple target mRNAs were involved, and they have versatile roles by functional enrichment analysis. Ac-cording to actual expression datasets in the study, compared to deregulated miRNAs, these theoretical target mRNAs showed various expression patterns. The consistent or inconsistent expression was mainly derived from complex, mul-tiple, flexible and alternative regulatory relationships between miRNA and mRNA. Further, miRNA/mRNA and lncRNA were completely surveyed based on their location distributions on human chromosomes. Many miRNA-lncRNA and mRNA-lncRNA pairs always were located on the same strand or different strands in the specific genomic region. Due to the location distributions, they might have partly or completely overlapped regions or they could be reverse complementarily binding. These miRNA/mRNA-lncRNA pairs showed consistent or inconsistent expression pat-terns, although they might have functional relationships through reverse complementarily binding events. Moreover, we also detected and analyzed various isomiRs from a given miRNA locus, including those isomiRs with 3’ additional non-template nucleotides. These isomiRs, especially for those 5’ isomiRs with the new “seed sequences” through “seed shifting” events, maybe have potential biological roles as well as isomiR repertoire and their expression patterns. The integrative analysis provides potential functional relationships between miRNA, lncRNA and mRNA across different datasets. The complex and various expression patterns suggest a robust regulatory network across different regulatory molecules and their targets.
Highlights
As important players of gene regulation, non-coding RNAs, have attracted considerable interests in many fields
High-throughput datasets of miRNA, long non-coding RNAs (lncRNAs) and mRNA were obtained from HepG2 and L02 cells applying Solexa sequencing platform and microarray technologies, respectively. miRNAs were identified from the raw miRNA datasets using Novoalign software (v2.07.11, http://www.novocraft.com) based on the known human miRNA precursors in the miRBase database (Release 18.0, http://www.mirbase.org/) [3]
The self-developed scripts were used to survey and obtain potential relationships between mRNA-miRNA, miRNAlncRNA and mRNA-lncRNA based on location distributions of aberrantly expressed ncRNA and mRNA profiles
Summary
As important players of gene regulation, non-coding RNAs (ncRNAs), have attracted considerable interests in many fields. LncRNAs have a broad range of biological roles in regulation of expression of genes and chromosomes. As potential regulators, they contribute to various basic cellular functions, such as cell proliferation, differentiation, death and tumorigenesis [2]. Concerning the potential relationships between different molecules, especially for their contributions to complex regulation network in multiple biological processes, cross-platform analysis has been a new hot focus. Based on potential positional and functional relationships between different molecules, we developed a method to integrative analyze datasets of ncRNA-mRNA from different cells applying highthrough-put technologies. The sequence and potential functional correlations and expression profiles of different RNA molecules can provide more complex interaction and biological roles across molecules in vivo. The integrative analysis method will systematically reveal the complex relationships in regulatory network and contributions in tumorigenesis
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