Network Analysis of MicroRNAs, Transcription Factors, Target Genes and Host Genes in Human Breast Cancer.

Abstract

This study constructs three regulatory networks of microRNAs (miRNAs) and genes in breast cancer (BC), and the abnormally expressed network may be the fault graph of BC’s canceration, which helps us identify pathogenesis of BC. Scientists have identified genes and miRNAs as decisive biological factors in progression of BC. Insufficiently, research data of genes and miRNAs is unorganized and scattered, which made regulatory mechanism of BC still indeterminate. In the current study, we didn’t only investigate one or several elements (miRNAs, TFs, target genes and host genes) associated with morbidity of BC. Instead, we systematically studied regulatory interactions among the whole elements relevant to BC and important regulatory pathways during BC’s canceration. Then three regulatory networks (including the abnormally expressed network, related network and global network) are hierarchically constructed at three levels, aiming at analyzing significant miRNA-gene signaling pathways at the macroscopic level. Results shows the abnormally expressed network contains substantial faulty regulations between miRNAs and genes when BC occurs, and it may be underlying fault graph of BC’s canceration. Significantly, if medical measure can be taken to correct each faulty regualtion to normal regulation, thus each genes and miRNAs will return to its normal expression level, and canceration of BC may be prevented and not occur. Furthermore, regulatory networks contain massive self-adaption feedbacks, which helps to understand the regulatory mechanism of BC. In conslusion, these networks, especially the abnormally expressed network, offers a systematical explanation about BC’s pathogenesis, which may aid future research and therapy of BC.