let-۷c and miR-۱۳۰b Play Regulatory Rolein Dysplasia Progressing to Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) is one ofthe most common neoplasms of the head and neck region, andit has a poor prognosis. MicroRNAs (miRNAs) play an importantrole in different biological processes related to cancer (۱,۲).This study aimed to reconstruct the miRNA-mRNA regulatorynetwork from dysplasia to OSCC.Materials and Methods: Gene expression profiles (GSE۳۰۷۸۴)were downloaded from the GEO database. Differentially expressedgenes (DEGs) were analyzed with TranscriptomeAnalysis Console (TAC) software in two groups: OSCC anddysplasia compared with the control group and filtered with Pvalue< ۰.۰۵ and |log fold change| > ۲. Finally, after drawing theVenn diagram and removing common genes, only dysplasiaspecificgenes were selected. We established a protein-proteininteraction (PPI) network of the DEGs through the STRINGdatabase and functional and pathway enrichment analyses were performed by the ToppGene database. The PPI network wasanalyzed with Gephi software. After identifying dysplasia-specificmiRNAs in the ToppGene database, we reconstructed themiRNA-mRNA regulatory network using Cytoscape. Next, thehighest degree miRNAs were determined.Results: A total of ۱۰۷ DEGs were identified which were indysplasia. Furthermore, hub mRNAs (DSG۱, LORICRIN, KRT۶A,KRT۱۰, KRT۲, PKP۱) in PPI network and hub miRNAs(let-۷c, miR-۱۳۰b, miR-۴۵۴, miR-۲۷b, miR-۳۰۱b) in Regulatorynetwork were also identified. Gene ontology analysisshowed significant enrichment of genes such as keratinizationand keratinocyte differentiation in biological processes, serinetypeendopeptidase activity and serine hydrolase activity inmolecular function. Formation of the cornified envelope andKeratinization pathways play a critical role in dysplasia.Conclusion: This study reconstructed the miRNA-mRNAregulatory network that may play a crucial role in dysplasiaprogressing to OSCC. Our findings suggested that dysplasiaspecificgenes showed participation in the Keratinization pathwaywhich may play the most prominent role in dysplasia progressionto OSCC.