In-silico, interactomic based screening and identification of differentially expressed miRNAs in oral submucous fibrosis and oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer, and its progression follows mostly the transition from oral potentially malignant disorders (OPMDs). Oral submucous fibrosis (OSMF) is a critical OPMD that transforms to OSCC in around 5% of cases; it's detected at later stages when it turns to invasive cancer. microRNA's (miRNAs) are essential regulators of many tumorigenic processes with aberrant expression profiles observed in many cancers. miRNAs are studied and identified as possible diagnostic markers in many cancers. Therefore, they may also serve as risk stratification biomarkers in OSCC transformed from OSMF. The present study performed a three-phase screening for differentially expressed microRNAs in OSCC and OSMF datasets from publicly available databases. The first phase includes screening dysregulated miRNAs in OSCC from cancer-specific miRNA Databases such as miRCancer, miRDB, and miRWalk, and fourteen common miRNAs obtained from these databases. Secondly, the OSCC differentially expressed miRNAs obtained from NCBI-GEO microarray datasets. Eleven out of earlier fourteen miRNAs had aberrant expressions with Fold change >1.5 and P-value <0.05. Further, out of the above eleven miRNA's five, i.e., miR-375, miR-451, miR-221, miR-133a, and miR-133b, were shared between the OSMF and OSCC differentially expressed miRNAs. Differentially expressed miRNAs for OSMF obtained from miRWalk, a disease-specific miRNAs database for predicted and validated datasets. The target gene search for these five miRNAs was performed using TargetScan, followed by the interactomic analysis to study the functional importance of these miRNA targets in tumorigenesis. These miRNA targets were extensively enriched mechanisms such as epithelial-mesenchymal transition, cell-cell adhesion, cell cycle regulation, which are already studied as critical pathways involved in OSMF tumorigenesis. Therefore, these five screened miRNAs may serve as risk stratification biomarkers with further validation in larger categorical datasets and clinical samples.