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Ajay Francis Christopher, Mridula Gupta and Parveen Bansal
Baba Farid University of Health Sciences, India
Posters & Accepted Abstracts: J Clin Trials
Introduction: Although substantial advancement has been achieved in the techniques and therapies related to oral squamous cell carcinoma (OSCC). Still, there is requisite for the novel approaches to reveal the various pathways and their regulators to treat the disease. We aim to find out key genes and miRNAs involved in positive regulation of cell proliferation and negative apoptosis. Method: To analyze the genes, differentially expressed OSCC genes were obtained from various published papers and databases. Gene ontology (GO) was done using STRING v 10 to obtain genes involved in cell proliferation (CP) and apoptosis (AP) and their positive (+ve) and negative (-ve) regulations. Experimentally validated miRNA-target interactions (MTIs) were retrieved from miRTarBase. The target genes of miRNAs were predicted through utilizing tools TargetScan. Key miRNAs and genes were identified for cell proliferation, positive regulation cell proliferation and negative regulation of apoptosis using Cytoscape 3.3.0. Results: Twenty four genes were found to be regulating CP+ve and AP-ve. Micronome of CP, AP and its +ve and -ve regulator revealed 11 common miRNAs (miR-379-5p, miR-106b-3p, miR-208b-3p, miR-208a-3p, miR-504-5p, miR-33a-3p, miR-328-3p, miR-376c- 3p, miR-197-3p, miR-496 and miR-758-3p). The direct target of these miRNAs were EDN1, HSPA5; HIF1A, NFE2L2; CDKN1A; CDKN1A, ETS1; MDM2; RARB, GSK3B; SFRP1; DAPK1, TGFA; IL18; MDM2 and MDM2 respectively. Gene Ontology based network of CP, CP+ve and AP-ve revealed CDKN1A as key regulator of these pathways. The Target Scan showed direct miRNAmRNA interactions of mir-208a-3p and mir-208b-3p with CDKN1A. Conclusion: miR208a/b-3p controls both positive regulation of cell proliferation and negative regulation of apoptosis via CDKN1A gene which are potential candidate for drug targets in OSCC.
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