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Altered PLAU Expression in Porphyromonas gingivalis-Treated Human Immortalised Oral Epithelial Cells and Its Putative Role in Head and Neck Squamous Cell Carcinoma

Articles in Press

Document Type : Original Article(s)

Authors

1 Department of Microbiology, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India.

2 Clinical Genetics Lab, Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India

10.30476/mejc.2026.106070.2255

Abstract

Background: Porphyromonas gingivalis, a key pathogen in periodontitis, has been implicated in oral carcinogenesis. The present study investigated the dysregulated genes in human oral epithelial cells (HOEC) treated with P. gingivalis (Pg) and explored their potential involvement in the development of head and neck squamous cell carcinoma (HNSCC).
Method: A computational design, using GEOmnibus data was employed to extract key information on differentially expressed genes (DEGs) in HOEC treated with Pg. A curated list of the top 20 DEGs was then examined for their gene expression profiles and survival rates using the UALCAN database. To explore gene enrichment and protein interaction networks, the Metascape and STRING databases were used. Additionally, the effect of microRNA on the expression profiles of candidate genes shared by both phenotypes was examined using the miRDB portal.
Results: Among the 20 genes queried, the PLAU gene was found to be upregulated in both the Pg-treated cells and the HNSCC dataset. The high expression of this gene correlated with poor prognosis in HNSCC patients. Furthermore, the microRNA hsa-miR-23b-3p, identified as targeting PLAU, was significantly downregulated, resulting in poor prognosis in HNSCC patients.
Conclusion: Our study reveals that Pg infection induced significant alterations in the gene expression in HOEC. The PLAU gene was identified as an important gene that demonstrated a putative association with periodontal disease and HNSCC. The influence of epigenetic markers, such as non-coding RNAs, and the methylation profile of the gene requires further investigation.

Highlights

Vijayashree Priyadharsini Jayaseelan (google scholar)

Keywords

Main Subjects

Please cite this article as: Kannan A, Jayaseelan VP. Altered PLAU Expression in Porphyromonas gingivalis-Treated Human Immortalised Oral Epithelial Cells and Its Putative Role in Head and Neck Squamous Cell Carcinoma. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.106070.2255.

References
  1. Aghili S, Rahimi H, Hakim LK, Karami S, Soufdoost RS, Oskouei AB, et al. Interactions between oral microbiota and cancers in the aging community: A narrative review. Cancer Control. 2024;31:10732748241270553. doi: 10.1177/10732748241270553. PMID: 39092988; PMCID: PMC11378226.
  2. Kashyap B, Kullaa A. Salivary metabolites produced by oral microbes in oral diseases and oral squamous cell carcinoma: A review. 2024;14(5):277. doi: 10.3390/metabo14050277. PMID: 38786754; PMCID: PMC11122927.
  3. Farhad SZ, Karbalaeihasanesfahani A, Dadgar E, Nasiri K, Esfahaniani M, Nabi Afjadi M. The role of periodontitis in cancer development, with a focus on oral cancers. Mol Biol Rep. 2024;51(1):814. doi: 10.1007/s11033-024-09737-6. PMID: 39008163.
  4. Villar A, Mendes B, Viègas M, de Aquino Alexandre AL, Paladini S, Cossatis J. The relationship between periodontal disease and cancer: Insights from a Systematic Literature Network Analysis. Cancer Epidemiol. 2024;91:102595. doi: 10.1016/j.canep.2024.102595. PMID: 38878682.
  5. Woo BH, Kim DJ, Choi JI, Kim SJ, Park BS, Song JM, et al. Oral cancer cells sustainedly infected with Porphyromonas gingivalis exhibit resistance to Taxol and have higher metastatic potential. 2017;8(29):46981-92. doi: 10.18632/oncotarget.16550. PMID: 28388583; PMCID: PMC5564538.
  6. Groeger SE, Hudel M, Zechel-Gran S, Herrmann JM, Chakraborty T, Domann E, et al. Recombinant Porphyromonas gingivalis W83 FimA alters immune response and metabolic gene expression in oral squamous carcinoma cells. Clin Exp Dent Res. 2022;8(4):976-87. doi: 10.1002/cre2.588. PMID: 35570325; PMCID: PMC9382057.
  7. Geng F, Liu J, Guo Y, Li C, Wang H, Wang H, et al. Persistent exposure to Porphyromonas gingivalispromotes proliferative and invasion capabilities, and tumorigenic properties of human immortalized oral epithelial cells. Front Cell Infect Microbiol. 2017;7:57. doi: 10.3389/fcimb.2017.00057. PMID: 28286742; PMCID: PMC5323389.
  8. He B, Cao Y, Zhuang Z, Deng Q, Qiu Y, Pan L, et al. The potential value of oral microbial signatures for prediction of oral squamous cell carcinoma based on machine learning algorithms. Head Neck. 2024;46(7):1660-70. doi: 10.1002/hed.27795. PMID: 38695435.
  9. Belibasakis GN, Seneviratne CJ, Jayasinghe RD, Vo PT, Bostanci N, Choi Y. Bacteriome and mycobiome dysbiosis in oral mucosal dysplasia and oral cancer. Periodontol 2000. 2024;96(1):95-111. doi: 10.1111/prd.12558. PMID: 38501658; PMCID: PMC11579824.
  10. Bs A, P A, As SG, A P, J VP. Analysis of differentially expressed genes in dysplastic oral keratinocyte cell line and their role in the development of HNSCC. J Stomatol Oral Maxillofac Surg. 2024;125(4S):101928. doi: 10.1016/j.jormas.2024.101928. PMID: 38815724.
  11. M D, P A, Smiline Girija AS, A P, Priyadharsini J V. Differential gene expression profile in Porphyromonas gingivalistreated human gingival keratinocytes and their role in the development of HNSCC. J Oral Biol Craniofac Res. 2025;15(1):48-56. doi: 10.1016/j.jobcr.2024.11.007. PMID: 39717877; PMCID: PMC11664403.
  12. Shanmugam SB, Vijayashree Priyadharsini J, Anitha P, Smiline Girija AS, Paramasivam A. Dysregulated genes in HIGK-treated  nucleatum and their possible association with HNSCC. Mol Biol Res Commun. 2025;14(1):59-71. doi: 10.22099/mbrc.2024.50171.1982. PMID: 39744516; PMCID: PMC11624608.
  13. Liu M, Shao J, Zhao Y, Ma B, Ge S. Porphyromonas gingivalisevades immune clearance by regulating lysosome efflux. J Dent Res. 2023;102(5):555-64. doi: 10.1177/00220345221146097. PMID: 36800907.
  14. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607-D613. doi: 10.1093/nar/gky1131. PMID: 30476243; PMCID: PMC6323986.
  15. Mi H, Thomas P. PANTHER pathway: an ontology-based pathway database coupled with data analysis tools. Methods Mol Biol. 2009;563:123-40. doi: 10.1007/978-1-60761-175-2_7. PMID: 19597783; PMCID: PMC6608593.
  16. Mi H, Ebert D, Muruganujan A, Mills C, Albou LP, Mushayamaha T, et al. PANTHER version 16: a revised family classification, tree-based classification tool, enhancer regions and extensive API. Nucleic Acids Res. 2021;49(D1):D394-D403. doi: 10.1093/nar/gkaa1106. PMID: 33290554; PMCID: PMC7778891.
  17. Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6. PMID: 30944313; PMCID: PMC6447622.
  18. Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: An update to the integrated cancer data analysis platform. 2022;25:18-27. doi: 10.1016/j.neo.2022.01.001. PMID: 35078134; PMCID: PMC8788199. 
  19. Győrffy B. Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors. Innovation (Camb). 2024;5(3):100625. doi: 10.1016/j.xinn.2024.100625. PMID: 38706955; PMCID: PMC11066458.
  20. Bartha Á, Győrffy B. TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues. Int J Mol Sci. 2021;22(5):2622. doi: 10.3390/ijms22052622. PMID: 33807717; PMCID: PMC7961455.
  21. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res. 2013;41(Database issue):D991-5. doi: 10.1093/nar/gks1193. PMID: 23193258; PMCID: PMC3531084.
  22. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. 2017;19(8):649-58. doi: 10.1016/j.neo.2017.05.002. PMID: 28732212; PMCID: PMC5516091. 
  23. Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127-D131. doi: 10.1093/nar/gkz757. PMID: 31504780; PMCID: PMC6943051. 
  24. Liu W, Wang X. Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biol. 2019;20(1):18. doi: 10.1186/s13059-019-1629-z. PMID: 30670076; PMCID: PMC6341724.
  25. Zhang X, Wang X, Wu J, Wang M, Hu B, Qu H, et al. The global burden of periodontal diseases in 204 countries and territories from 1990 to 2019. Oral Dis. 2024;30(2):754-68. doi: 10.1111/odi.14436. PMID: 36367304.
  26. Yuan Q, Wu H, Tan H, Wang X, Cao Y, Chen G. Oral microbial dysbiosis driven by periodontitis facilitates oral squamous cell carcinoma progression. Cancers (Basel). 2025;17(13):2181. doi: 10.3390/cancers17132181. PMID: 40647479; PMCID: PMC12249316.
  27. Yáñez L, Soto C, Tapia H, Pacheco M, Tapia J, Osses G, et al. Co-culture ofP. gingivalis and F. nucleatum  synergistically elevates IL-6 expression via TLR4 signaling in oral keratinocytes. Int J Mol Sci. 2024;25(7):3611. doi: 10.3390/ijms25073611. PMID: 38612423; PMCID: PMC11011619.
  28. Ha NH, Woo BH, Kim DJ, Ha ES, Choi JI, Kim SJ, et al. Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties. Tumour Biol. 2015;36(12):9947-60. doi: 10.1007/s13277-015-3764-9. PMID: 26178482.
  29. Lee J, Roberts JS, Atanasova KR, Chowdhury N, Han K, Yilmaz Ö. Human primary epithelial cells acquire an epithelial-mesenchymal-transition phenotype during long-term infection by the oral opportunistic pathogen, Porphyromonas gingivalis. Front Cell Infect Microbiol. 2017;7:493. doi: 10.3389/fcimb.2017.00493. PMID: 29250491; PMCID: PMC5717492.
  30. Chen G, Sun J, Xie M, Yu S, Tang Q, Chen L. PLAU promotes cell proliferation and epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Front Genet. 2021;12:651882. doi: 10.3389/fgene.2021.651882. PMID: 34093649; PMCID: PMC8173099.
  31. Hamada M, Inaba H, Nishiyama K, Yoshida S, Yura Y, Matsumoto-Nakano M, et al. Transcriptomic analysis of Porphyromonas gingivalis-infected head and neck cancer cells: Identification of PLAU as a candidate prognostic biomarker. J Cell Mol Med. 2024;28(4):1-18. doi: 10.1111/jcmm.18167. PMID: 38363001; PMCID: PMC10870695.
  32. Lu Z, Cao R, Geng F, Pan Y. Persistent infection with Porphyromonas gingivalis increases the tumorigenic potential of human immortalised oral epithelial cells through ZFP36 inhibition. Cell Prolif. 2024;57(6):e13609. doi: 10.1111/cpr.13609. PMID: 38351596; PMCID: PMC11150143.
  33. Shi K, Zhou J, Li M, Yan W, Zhang J, Zhang X, et al. Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA. Biochim Biophys Acta Mol Basis Dis. 2024;1870(2):166965. doi: 10.1016/j.bbadis.2023.166965. PMID: 38000776.
  34. Fang L, Che Y, Zhang C, Huang J, Lei Y, Lu Z, et al. PLAU directs conversion of fibroblasts to inflammatory cancer-associated fibroblasts, promoting esophageal squamous cell carcinoma progression via uPAR/Akt/NF-κB/IL8 pathway. Cell Death Discov. 2021;7(1):32. doi: 10.1038/s41420-021-00410-6. PMID: 33574243; PMCID: PMC7878926.
  35. K P A, Usman P P AS, Sekar D. OIP5-AS1 expression profiles in different stages of oral squamous cell carcinoma. Arch Oral Biol. 2025;180:106403. doi: 10.1016/j.archoralbio.2025.106403. PMID: 41014896.
  36. Thomas P, Selvakumar SC, Preethi KA, Sekar D. Expression profiling of signal transducer and activator of transcription3 in oral squamous cell carcinoma in south Indian population. Minerva Dent Oral Sci. 2024;73(1):37-44. doi: 10.23736/S2724-6329.23.04840-4. PMID: 37878241.
  37. Neralla M, S H, Selvakumar SC, Preethi KA, Sekar D. Gene expression analysis of microRNA-1285 in the South Indian oral squamous cell carcinoma population. Minerva Dent Oral Sci. 2024;73(5):249-55. doi: 10.23736/S2724-6329.23.04798-8. PMID: 37410075.
  38. Muthumanickam P, Ramasubramanian A, Pandi C, Kannan B, Pandi A, Ramani P, et al. The novel m6A writer methyltransferase 5 is a promising prognostic biomarker and associated with immune cell infiltration in oral squamous cell carcinoma. J Oral Pathol Med. 2024;53(8):521-9. doi: 10.1111/jop.13568. PMID: 38939970.
  39. Hu J, Sun Z, Hu K, Tang M, Sun S, Fang Y, et al. Over-expression of Hsa-miR-23b-3p suppresses proliferation, migration, invasion and epithelial-mesenchymal transition of human cervical cancer CasKi cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2020;36(11):983-9. Chinese. PMID: 33210592.
  40. Campos-Viguri GE, Peralta-Zaragoza O, Jiménez-Wences H, Longinos-González AE, Castañón-Sánchez CA, Ramírez-Carrillo M, et al. MiR-23b-3p reduces the proliferation, migration and invasion of cervical cancer cell lines via the reduction of c-Met expression. Sci Rep. 2020;10(1):3256. doi: 10.1038/s41598-020-60143-x. PMID: 32094378; PMCID: PMC7039958.
Middle East Journal of Cancer

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Available Online from 01 October 2026
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