Exploring miRNA Sponge Networks of Breast Cancer by Combining miRNA-disease-lncRNA and miRNA-target Networks

Abstract

Background: Recently, ample researches show that microRNAs (miRNAs) not only interact with coding genes but interact with a pool of different RNAs. Those RNAs are called miRNA sponges, including long non-coding RNAs (lncRNAs), circular RNA, pseudogenes and various messenger RNAs. Understanding regulatory networks of miRNA sponges can better help researchers to study the mechanisms of breast cancers. Objective: We develop a new method to explore miRNA sponge networks of breast cancer by combining miRNAdisease-lncRNA and miRNA-target networks (MSNMDL). Method: Firstly, MSNMDL infers miRNA-lncRNA functional similarity networks from miRNAdisease- lncRNA networks. Secondly, MSNMDL forms lncRNA-target networks by using lncRNA to replace the role of matched miRNA in miRNA-target networks according to the lncRNA-miRNA pair of miRNA-lncRNA functional similarity networks. And MSNMDL only retains the genes of breast cancer in lncRNA-target networks to construct candidate miRNA sponge networks. Thirdly, MSNMDL merges these candidate miRNA sponge networks with other miRNA sponge interactions and then selects top-hub lncRNA and its interactions to construct miRNA sponge networks. Results: MSNMDL is superior to other methods in terms of biological significance and its identified modules might act as module signatures for prognostication of breast cancer. Conclusion: MiRNA sponge networks identified by MSNMDL are biologically significant and are closely associated with breast cancer, which makes MSNMDL a promising way for researchers to study the pathogenesis of breast cancer.