Abstract
Oral squamous cell carcinoma (OSCC) is one of the leading cancers with poor disease survival rate. Herein, we explored molecular basis, in silico identification and in vitro verification of genes associated with OSCC. Five gene expression series including, GSE30784, GSE13601, GSE9844, GSE23558 and GSE37991 were screened for differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched by cluster Profiler. Further, protein–protein interaction network was analysed and hub genes were verified. A total of 6476 (up-regulated: 2848; down-regulated: 3628) DEGs were identified among OSCC patients and healthy controls. Gene Ontology analysis indicated DEGs enrichment in cellular motility, invasion and adhesion processes. KEGG analysis revealed enrichment of PI3K-Akt signalling, focal adhesion and regulation of actin cytoskeleton pathways. Subsequently, nine DEGs including APP, EHMT1, ACACB, PCNA, PLAU, FST, HMGA2, LAMC2 and SPP1 were correlated with TCGA expression data along with significant association towards patient’s survival, recognized as hub genes. This dysregulated mRNA signature of genes was validated in two OSCC cell lines with an anti-cancer agent, fisetin. Fisetin inhibited the expression of APP, EHMT1, PCNA, PLAU, FST, HMGA2, LAMC2, SPP1 and upregulated the expression of ACACB gene which were associated with growth inhibition of both the OSCC cell lines. The regulatory effect of fisetin supported crucial role of nine hub genes identified in OSCC. This study signified that hub genes and pathways might influence the aggressiveness of OSCC. Thus, the proposed hub genes could be potential diagnostic biomarker and drug targets for OSCC.
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Acknowledgements
The authors are thankful to CIF, JNU and ICMR-AIIMS Computational Genomics Centre, New Delhi for helping in present work.
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The work is supported by DPRP, Department of Science and Technology (DST), India, and DST-PURSE, UGC-RN, UPE-2 from Jawaharlal Nehru University, New Delhi. M.Y. is supported by a fellowship from DST-INSPIRE (IF160971), New Delhi, India.
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Execution of research method, bioinformatics analysis, result interpretation, experimental validation, and original draft preparation were performed by Monika Yadav. Dr. Pradhan has done bioinformatics analysis, result interpretation, and visualization. Conceptualization, supervision, reviewing, and final editing of manuscript were accomplished by Dr. Singh.
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Yadav, M., Pradhan, D. & Singh, R.P. Integrated analysis and identification of nine-gene signature associated to oral squamous cell carcinoma pathogenesis. 3 Biotech 11, 215 (2021). https://doi.org/10.1007/s13205-021-02737-4
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DOI: https://doi.org/10.1007/s13205-021-02737-4