Discovering MicroRNA-Regulatory Modules in Multi-Dimensional Cancer Genomic Data: A Survey of Computational Methods

MicroRNAs (miRs) are small single-stranded noncoding RNA that function in RNA silencing and post-transcriptional regulation of gene expression. An increasing number of studies have shown that miRs play an important role in tumorigenesis, and understanding the regulatory mechanism of miRs in this gene regulatory network will help elucidate the complex biological processes at play during malignancy. Despite advances, determination of miR-target interactions (MTIs) and identification of functional modules composed of miRs and their specific targets remain a challenge. A large amount of data generated by high-throughput methods from various sources are available to investigate MTIs. The development of data-driven tools to harness these multi-dimensional data has resulted in significant progress over the past decade. In parallel, large-scale cancer genomic projects are allowing new insights into the commonalities and disparities of miR-target regulation across cancers. In the first half of this review, we explore methods for identification of pairwise MTIs, and in the second half, we explore computational tools for discovery of miR-regulatory modules in a cancer-specific and pan-cancer context. We highlight strengths and limitations of each of these tools as a practical guide for the computational biologists.