miRNA-mRNA network detects hub mRNAs and cancer specific miRNAs in lung cancer

Abstract

MicroRNA expression profiles can improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. In this paper, we undertook to develop a miRNA-mRNA network and uncover unique growth suppressive miRNAs in lung cancer using microarray data. The miRNA-mRNA network was developed based on a bipartite graph theory approach, and a number of miRNA-mRNA modules have been identified to mine associations between miRNAs and mRNAs. From the network, we identified totally 29 protective miRNA-mRNA regulatory modules, since we restricted our search to protective miRNAs. Subsequently we analyzed the pathways for the target genes in the protective miRNA-mRNA modules using Pathway-Express. The miRNA-mRNA network efficiently detects hub mRNAs deregulated by the protective miRNAs and identifies cancer specific miRNAs in lung cancer. From the pathway analysis results, the ECM receptor pathway, Focal adhesion pathway and cell adhesion molecules pathway seem to be more interesting to investigate, since these pathways were related to all the ten protective miRNAs. Furthermore, protective miRNA target analysis revealed that genes VCAN, SIL, CD44 and MMP14 were found to have an important role in these pathways. Hence, it was inferred that these genes can be important putative targets for those protective miRNAs. A greater understanding of the mechanisms regulating VCAN, SIL, CD44 and MMP14 expression and activity will assist in the development of specific inhibitors of cancer cell metastasis. Thus these observations are expected to have an intense implication in cancer and may be useful for further research.