Identifying miRNA synergism using multiple-intervention causal inference

Abstract

ConclusionsTaken together, the results imply that miRsyn is a promising framework for identifying miRNA synergism, and it could enhance the understanding of miRNA synergism in breast cancer. Keywords miRNA -miRNA synergistic network -miRNA synergistic module -Multiple intervention causal inference -Breast cancer Background MicroRNAs (miRNAs) are a class of short non-coding RNAs with ~23 nucleotides (nts) in length. They play an important regulatory role at the post-transcriptional level by targeting messenger RNAs (mRNAs) for degradation or translation repression [1].Previous studies have demonstrated that miRNAs play a crucial role in regulating gene expression involved in diverse biological processes, including cell proliferation, cell death, cell apoptosis and human cancers [2][3][4]. Generally, the relationships between miRNAs and their target genes are not one-to-one but many-to-many, indicating cooperative regulation of miRNAs. The co-regulation of miRNAs has been accepted and confirmed by cross-linking and immunoprecipitation technologies, and may be related to human complex diseases [5]. Therefore, studying miRNA synergism can greatly help to understand the synergistic regulation mechanism of miRNAs in human diseases.Until now, a number of computational methods have been proposed to identify miRNA synergism. These methods can be divided into three different categories: (1) sequence-based [6-8], (2) correlation-based [9][10][11][12][13][14], and (3) causality-based [15]. In the first category, the sequence data mainly includes putative miRNA-target interactions and protein-protein interactions (PPIs). For each candidate miRNA-

Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer

“…The complexity of such networks results from the multiplicity of miRNA–target interactions, which often engage in reciprocal feedback and feedforward loops (55,56). Hence, network approaches have been applied to infer cooperative regulation among miRNAs (57,58). Xu et al.…”