Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ
Main Article Content
Keywords
Analysis, Germ, potential, human
Abstract
Background: Pathogenesis of most odontogenic tumors is not well established. It is important to identify various genetic deregulations and molecular alterations. Common signaling pathways between ameloblastoma and human tooth germ is yet to be well established. This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and human tooth germ.
Aim: To analyze the genes commonly expressed in human tooth germ and ameloblastoma for better understanding the molecular pathogenesis of ameloblastoma.
Materials and methods: This is an in-silico study. GeneCards database was used for this study. The database was used to identify important genes expressed in the formation of human tooth germ and ameloblastoma. The potential candidate genes were then mapped using an online program STRING (version 11.5). This identified the interaction of networks between the protein-coding genes. The genes which showed a high degree of confidence were included and their direct and indirect interactions were evaluated. Each gene interaction was scored to produce an overall association score. The genes which displayed the highest WNL score were mentioned as leader genes.
Results: GeneCards and STRING analysis showed a final count of 10 genes that were commonly expressed in ameloblastoma and human tooth germ were included. These were : IGF1 , STAT1 , TLR2 , BRAF , IGF2 , ERK2 , ERK1 , NFkappaB , MEK2 and MEK1. From the WNL analysis, ameloblastoma, the highest WNL values were identified in genes BRAF V600E, MAPK, STAT1 and NFKappaB, The most relevant WNL values for human tooth germ are IGF1, IGF2, TLR1, TLR2 , STAT1 and NKKappaB1.
Conclusion: STAT 1 and NFKappaB together help in tumor cell proliferation and cell survival. Numerous targeted therapies have been produced against these genes. Further in vitro molecular analysis such as microarray are needed for proper application of these therapies.
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7. Darnell, J. E., Jr, I. M. Kerr, and G. R. Stark. 1994. “Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins.” Science 264 (5164): 1415–21.
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11. Gomes, Carolina Cavalieri, Alessandra Pires Duarte, Marina Gonçalves Diniz, and Ricardo Santiago Gomez. 2010. “Review Article: Current Concepts of Ameloblastoma Pathogenesis.” Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 39 (8): 585–91.
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of Biological Chemistry. https://doi.org/10.1074/jbc.271.10.5947.
14. Horvath, C. M., G. R. Stark, I. M. Kerr, and J. E. Darnell. 1996. “Interactions between STAT and Non-STAT Proteins in the Interferon-Stimulated Gene Factor 3 Transcription Complex.” Molecular and Cellular Biology. https://doi.org/10.1128/mcb.16.12.6957.
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16. Jenkins, Brendan John. 2014. “Transcriptional Regulation of Pattern Recognition Receptors by JAK/STAT Signaling, and the Implications for Disease Pathogenesis.” Journal of Interferon & Cytokine Research. https://doi.org/10.1089/jir.2014.0081.
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18. Lin, Sheng-Chieh, Yi-Chu Liao, Po-Ming Chen, Ya-Yu Yang, Yi-Hsiang Wang, Shiao-Lin Tung, Chi-Mu Chuang, et al. 2022. “Periostin Promotes Ovarian Cancer Metastasis by Enhancing M2 Macrophages and Cancer-Associated Fibroblasts via Integrin-Mediated NF-κB and TGF-β2 Signaling.” Journal of Biomedical Science 29 (1): 109.
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20. Mithra, and Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University. 2021. “Genetic Association of Bcl2 (rs2279115) Gene Polymorphism with Susceptibility to Oral Cancer - A Case Control Study in South Indian Population.” International Journal of Dentistry and Oral Science, July, 3431–34.
21. Mony, Ullas, and Vishnu Priya Veeraraghavan. 2022. “‘Rules’ to the Genetic Progression of Tumours Deciphered: Is It Time to Think Differently in Treating Oral Cancer Patients?” Oral Oncology 134 (November): 106111.
22. Morgan, Peter R. 2011. “Odontogenic Tumors: A Review.” Periodontology 2000 57 (1): 160–76.
23. Mosqueda-Taylor, Adalberto. 2008. “New Findings and Controversies in Odontogenic Tumors.” Medicina Oral, Patologia Oral Y Cirugia Bucal 13 (9): E555–58.
24. Ogasa, M. 2003. “Gastrin Activates Nuclear Factor kappaB (NFkappaB) through a Protein Kinase C Dependent Pathway Involving NFkappaB Inducing Kinase, Inhibitor kappaB (IkappaB) Kinase, and Tumour Necrosis Factor Receptor Associated Factor 6 (TRAF6) in MKN-28 Cells Transfected with Gastrin Receptor.” Gut. https://doi.org/10.1136/gut.52.6.813.
25. Orlando, B., N. Bragazzi, and C. Nicolini. 2013. “Bioinformatics and Systems Biology Analysis of Genes Network Involved in OLP (Oral Lichen Planus) Pathogenesis.” Archives of Oral Biology 58 (6): 664–73.
26. Pandiar, Deepak, Pratibha Ramani, P. M. Shameena, Reshma Poothakulath Krishnan, and K. Monica. 2022. “Adenoid Ameloblastoma: A Neglected Variant of Ameloblastoma or a Separate Entity?” Oral Oncology 125 (February): 105681.
27. Paramasivam, Arumugam. 2022. “Plasma Circulating Tumor DNA as a Molecular Marker for Oral Cancer.” Oral Oncology 130 (July): 105926.
28. Peng, Hong, Ting Ye, Lei Deng, Xiaofang Yang, Zheng Jiang, and Jinjun Guo. 2022. “Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis.” Canadian Journal of Gastroenterology & Hepatology 2022 (December): 8996203.
29. Philipsen, Hans P., and Peter A. Reichart. 2002. “Revision of the 1992-Edition of the WHO Histological Typing of Odontogenic Tumours. A Suggestion.” Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 31 (5): 253–58.
30. Pradeep, and Associate Professor, Department of Oral And Maxillofacial Surgery, Saveetha Dental college & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University. 2021. “Unicystic Ameloblastoma: Case Reports and Review of Literature Pradeep D.” International Journal of Dentistry and Oral Science, July, 3412–15.
31. Pradeep, and Senior Lecturer, Department of Conservative Dentistry and Endodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University. 2021. “Unicystic Mural Ameloblastoma: An Case Report and Review of Litrature.” International Journal of Dentistry and Oral Science, July, 3534–37.
32. Ramani, Pratibha, Reshma Poothakulath Krishnan, Deepak Pandiar, Aklesha Behera, and Abilasha Ramasubramanian. 2022. “Squamous Odontogenic Tumor like Proliferations in Dentigerous Cyst- a Great Mimicker.” Oral Oncology 125 (February): 105699.
33. Ramani, Pratibha, Reshma Poothakulath Krishnan, Deepak Pandiar, and Snega Thamilselvan. 2022. “A Rare Combined Motley Variety of Odontogenic Tumors - Hybrid Lesion or a New Entity?” Oral Oncology 124 (January): 105521.
34. Ramani, Pratibha, Deepak Pandiar, S. Gheena, and Reshma Poothakulath Krishnan. 2022. “Archegonous Cystic Odontoma: A Recently Described yet an under-Recognized Odontogenic Pathology.” Oral Oncology 127 (April): 105820.
35. Ramesh, Sindhu, and Professor, Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and technical Sciences, Saveetha University, Chennai, India. 2021. “Evaluation of Interleukin 6, Interleukin 8, TNF Alpha as Biomarkers for Pulpitis - in Vivo Study.” International Journal of Dentistry and Oral Science, February, 1655–60.
36. Rizzitelli, Alexandra, Nicolas R. Smoll, Michael P. Chae, Warren M. Rozen, and David J. Hunter-Smith. 2015. “Incidence and Overall Survival of Malignant Ameloblastoma.” PLOS ONE. https://doi.org/10.1371/journal.pone.0117789.
37. Sarode, Sachin C., Shailesh Gondivkar, Gargi S. Sarode, Amol Gadbail, and Monal Yuwanati. 2021. “Hybrid Oral Potentially Malignant Disorder: A Neglected Fact in Oral Submucous Fibrosis.” Oral Oncology 121 (October): 105390.
38. Sasikumar, P. K., Sheeja S. Varghese, Thanga Kumaran, and Sakthi Saranya Devi. 2020. “Meta-Analysis of Risk Association between Interleukin-17A Gene Polymorphism and Chronic Periodontitis.” Contemporary Clinical Dentistry 11 (1): 3–9.
39. Schindler, C., and J. E. Darnell. 1995. “TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway.” Annual Review of Biochemistry. https://doi.org/10.1146/annurev.bi.64.070195.003201.
40. Shen, Ziyi, Shengxiong Pu, Xing Cao, Ming Tang, Shenglin Wang, Dazhang Bai, and Guohui Jiang. 2022. “Bioinformatics and Network Pharmacology Analysis of Drug Targets and Mechanisms Related to the Comorbidity of Epilepsy and Migraine.” Epilepsy Research 189 (December): 107066.
41. Siar, Chong Huat, Shin Hin Lau, and Kok Han Ng. 2012. “Ameloblastoma of the Jaws: A Retrospective Analysis of 340 Cases in a Malaysian Population.” Journal of Oral and Maxillofacial Surgery. https://doi.org/10.1016/j.joms.2011.02.039.
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Published
May 13, 2023
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Sangamithra.S, Abilasha Ramasubramanian, Vijayashree Priyadharsini J, & Pratibha Ramani. (2023). Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ. Journal of Population Therapeutics and Clinical Pharmacology, 30(10), 259–266. https://doi.org/10.47750/jptcp.2023.30.10.030
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