Identify Biological Modules and Hub MiRNAs for Oral Squamous Cell Carcinomas

Oral squamous cell carcinomas (OSCC) is the most common head and neck cancer worldwide, with more than 300,000 new cases being diagnosed annually. Studies have shown that miRNAs are involved in the process of growth, differentiation, apoptosis, invasion and metastasis of OSCC tumor cells. How miRNAs work together to contribute to this process is still largely unknown. The goal of our study was to characterize the coexpression network of miRNAs and to identify the miRNA subnetworks (modules) that were significantly associated with the OSCC cancer status. We also searched hub miRNAs that might play a vital role in the development of OSCC. We applied the weighted gene co-expression network analysis (WGCNA) to the miRNA expression profile data from a paired design study contributed by Shiah et al. To account for the within-pair correlation, a linear mixed model (LMM) was constructed to test the associations of miRNA modules to cancer status. Two significant modules (turquoise module with 254 miRNAs and grey module with 309 miRNAs) were identified. The miRNA miR-let-7c was the hub miRNA in the turquoise module in terms of node degree. Finally, we used miRsystem to perform the target gene prediction and KEGG pathway enrichment analysis of miRNAs within the two modules. Interestingly, the two modules have similar sets of target genes so that the top 6 enriched KEGG pathways for the 2 modules were the same. Compared with the probe-wise test used by Shiah et al., we took the network approach and identified significant OSCC-associated miRNA modules, which could help uncover the mechanism that miRNAs interplay each other to contribute to OSCC.