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Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines

Year 2025, Volume: 9 Issue: 3, 331 - 337, 22.12.2025
https://doi.org/10.46332/aemj.1676536

Abstract

Purpose: Hematological malignancies have become a significant health concern due to their increasing incidence. This highlights the need for the identification of novel biomarkers and therapeutic targets. Budding Uninhibited by Benzimidazoles 3 (BUB3) is a mitotic checkpoint protein that regulates chromosome segregation during mitosis. Dysregulation of BUB3-related pathways has been associated with tumor development and disease progression. This study aims to investigate the expression levels of BUB3 in Burkitt lymphoma (Raji) and T-cell leukemia (Jurkat) cell lines and to evaluate its potential as a biomarker and therapeutic target in hematological cancers.

Materials and Methods: BUB3 expression levels were analyzed in various cancer cell lines using the BioGPS database. Additionally, a protein-protein interaction (PPI) network was constructed via the STRING database to evaluate BUB3's interactions with cell cycle-related molecules. To validate the bioinformatics results, BUB3 expression was quantitatively measured by RT-qPCR in Raji, Jurkat, and control HaCaT (human keratinocyte) cell lines.

Results: RT-qPCR analysis revealed significantly was increased BUB3 expression in Raji and Jurkat cells compared to the HaCaT control group. PPI analysis indicated that BUB3 interacts with proteins involved in cell cycle regulation, apoptosis, and proliferation.

Conclusion: BUB3 is overexpressed in hematological malignancies and may play a role in tumor biology. Therefore, BUB3 could serve as a potential prognostic biomarker and therapeutic target. Further in vivo studies are needed to confirm its clinical relevance.

Ethical Statement

Since this was an in vitro study, ethics committee approval was not required.

Project Number

-

References

  • 1. Zhang N, Wu J, Wang Q, et al. Global burden of hematologic malignancies and evolution patterns over the past 30 years. Blood Cancer J. 2023;13(1):82.
  • 2. Malfona F, Testi AM, Chiaretti S, Moleti ML. Refractory Burkitt Lymphoma: Diagnosis and Interventional Strategies. Blood Lymphat Cancer. 2024;14:1-15.
  • 3. Fang H, Wang W, Medeiros LJ. Burkitt lymphoma. Hum Pathol. 2025;156:105703
  • 4. Bardelli V, Arniani S, Pierini V, et al. T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness. Genes (Basel). 2021;12(8):1118.
  • 5. Long Z, Wu T, Tian Q, et al. Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma. Aging (Albany NY). 2021;13(9):12395-12409.
  • 6. Wang C, Cheng D, Pan C, Wang C, Nie Z. Research progress of Bub3 gene in malignant tumors. Cell Biol Int. 2022;46(5):673-682.
  • 7. Wu C, Jin X, Tsueng G, Afrasiabi C, Su AI. BioGPS: Building your own mash-up of gene annotations and expression profiles. Nucleic Acids Res. 2016;44(1): 313-316.
  • 8. Wu C, Orozco C, Boyer J, et al. BioGPS: An extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol. 2009;17:10(11):130.
  • 9. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408.
  • 10. Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: customizable protein – protein networks, and functional characterization of user-uploaded gene / measurement sets. Nucleic Acids Res. 2021;49(1):605-612.
  • 11. Szklarczyk D, Franceschini A, Kuhn M, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011;39(1):561–568.
  • 12. Liu S, Lin Y, Wang Z. Causal relationships between body composition and hematological malignancies: a multivariable Mendelian randomization analysis. Cancer Causes Control. 2025;1–8.
  • 13. Wang L, Qin W, Huo YJ, et al. Advances in targeted therapy for malignant lymphoma. Signal Transduct Target Ther. 2020;6:5(1):15.
  • 14. Hosseini MS, Sanaat Z, Akbarzadeh MA, Vaez-Gharamaleki Y, Akbarzadeh M. Histone deacetylase inhibitors for leukemia treatment: current status and future directions. Eur J Med Res. 2024;29(1):514.
  • 15. Warren CD, Brady DM, Johnston RC, Hanna JS, Hardwick, KG, Spencer FA. Distinct chromosome segregation roles for spindle checkpoint proteins. Molecular Biology of the Cell. 2002;13(9):3029-3041.
  • 16. Acosta Davila JA, Hernandez De Los Rios A. An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites. Front. Cell. Infect. Microbiol. 2019; 9:24.
  • 17. Garaud S, Roufosse F, De Silva P, et al. FOXP1 is a regulator of quiescence in healthy human CD4⁺ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders. Eur. J. Immunol. 2017;47(1):168–179.
  • 18. Şenkal S, Burukçu D, Hayal TB et al. 3D culture of HaCaT keratinocyte cell line as an in vitro toxicity model. Trakya Univ J Nat Sci. 2022;23(2):211–220.
  • 19. Röwers F, Kühnl J, Wenzel J, Tiede S. HaCaT keratinocytes: An in vitro model for studies on epidermal homeostasis and tumorigenesis. Int J Mol Sci. 2021;22(23):12850

Raji ve Jurkat Hücre Hatlarında Mitotik Kontrol Noktası Geni BUB3 Ekspresyon Düzeylerinin Analizi

Year 2025, Volume: 9 Issue: 3, 331 - 337, 22.12.2025
https://doi.org/10.46332/aemj.1676536

Abstract

Amaç: Hematolojik maligniteler, artan insidansları nedeniyle önemli bir sağlık sorunu haline gelmiştir. Bu durum, yeni biyobelirteçlerin ve terapötik hedeflerin tanımlanmasını gerekli kılmaktadır. Budding Uninhibited by Benzimidazoles 3 (BUB3), mitoz sırasında kromozom segregasyonunu düzenleyen mitotik kontrol noktası proteinidir. BUB3 yolaklarındaki bozukluklar, tümör gelişimi ve hastalık progresyonu ile ilişkilendirilmiştir. Bu çalışmanın amacı, BUB3’ün Burkitt lenfoma (Raji) ve T-hücreli lösemi (Jurkat) hücre hatlarındaki ekspresyon seviyelerini belirlemek ve hematolojik kanserlerde olası bir biyobelirteç ve terapötik hedef olarak potansiyelini değerlendirmektir.

Araçlar ve Yöntem: BUB3 ekspresyon düzeyleri, BioGPS veritabanı kullanılarak çeşitli kanser hücre hatlarında analiz edilmiştir. Ayrıca, STRING veritabanı ile protein-protein etkileşim (PPI) ağı oluşturularak BUB3’ün hücre döngüsüyle ilişkili moleküllerle bağlantıları değerlendirilmiştir. Biyoinformatik bulguların doğrulanması amacıyla Raji, Jurkat ve kontrol olarak HaCaT hücre hatlarında RT-qPCR ile BUB3 ekspresyonu kantitatif olarak ölçülmüştür.

Bulgular: Raji ve Jurkat hücrelerinde BUB3 gen ekspresyonunun kontrol grubu olan HaCaT hücrelerine kıyasla anlamlı şekilde arttığını. RT-qPCR ile göstermiştir. PPI analizinde ise BUB3’ün hücre döngüsü, apoptoz ve proliferasyonla ilişkili proteinlerle etkileşim içinde olduğu saptanmıştır.

Sonuç: BUB3’ün hematolojik malignitelerde aşırı eksprese edildiği ve tümör biyolojisinde rol oynayabileceği belirlenmiştir. Bu nedenle BUB3, potansiyel bir prognostik biyobelirteç ve terapötik hedef adayı olabilir. Bu bulguların klinik olarak doğrulanabilmesi için ileri in vivo çalışmalar gereklidir.

Ethical Statement

Çalışma in vitro olduğundan etik kurul onayına gerek duyulmamıştır.

Project Number

-

References

  • 1. Zhang N, Wu J, Wang Q, et al. Global burden of hematologic malignancies and evolution patterns over the past 30 years. Blood Cancer J. 2023;13(1):82.
  • 2. Malfona F, Testi AM, Chiaretti S, Moleti ML. Refractory Burkitt Lymphoma: Diagnosis and Interventional Strategies. Blood Lymphat Cancer. 2024;14:1-15.
  • 3. Fang H, Wang W, Medeiros LJ. Burkitt lymphoma. Hum Pathol. 2025;156:105703
  • 4. Bardelli V, Arniani S, Pierini V, et al. T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness. Genes (Basel). 2021;12(8):1118.
  • 5. Long Z, Wu T, Tian Q, et al. Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma. Aging (Albany NY). 2021;13(9):12395-12409.
  • 6. Wang C, Cheng D, Pan C, Wang C, Nie Z. Research progress of Bub3 gene in malignant tumors. Cell Biol Int. 2022;46(5):673-682.
  • 7. Wu C, Jin X, Tsueng G, Afrasiabi C, Su AI. BioGPS: Building your own mash-up of gene annotations and expression profiles. Nucleic Acids Res. 2016;44(1): 313-316.
  • 8. Wu C, Orozco C, Boyer J, et al. BioGPS: An extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol. 2009;17:10(11):130.
  • 9. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408.
  • 10. Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: customizable protein – protein networks, and functional characterization of user-uploaded gene / measurement sets. Nucleic Acids Res. 2021;49(1):605-612.
  • 11. Szklarczyk D, Franceschini A, Kuhn M, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011;39(1):561–568.
  • 12. Liu S, Lin Y, Wang Z. Causal relationships between body composition and hematological malignancies: a multivariable Mendelian randomization analysis. Cancer Causes Control. 2025;1–8.
  • 13. Wang L, Qin W, Huo YJ, et al. Advances in targeted therapy for malignant lymphoma. Signal Transduct Target Ther. 2020;6:5(1):15.
  • 14. Hosseini MS, Sanaat Z, Akbarzadeh MA, Vaez-Gharamaleki Y, Akbarzadeh M. Histone deacetylase inhibitors for leukemia treatment: current status and future directions. Eur J Med Res. 2024;29(1):514.
  • 15. Warren CD, Brady DM, Johnston RC, Hanna JS, Hardwick, KG, Spencer FA. Distinct chromosome segregation roles for spindle checkpoint proteins. Molecular Biology of the Cell. 2002;13(9):3029-3041.
  • 16. Acosta Davila JA, Hernandez De Los Rios A. An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites. Front. Cell. Infect. Microbiol. 2019; 9:24.
  • 17. Garaud S, Roufosse F, De Silva P, et al. FOXP1 is a regulator of quiescence in healthy human CD4⁺ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders. Eur. J. Immunol. 2017;47(1):168–179.
  • 18. Şenkal S, Burukçu D, Hayal TB et al. 3D culture of HaCaT keratinocyte cell line as an in vitro toxicity model. Trakya Univ J Nat Sci. 2022;23(2):211–220.
  • 19. Röwers F, Kühnl J, Wenzel J, Tiede S. HaCaT keratinocytes: An in vitro model for studies on epidermal homeostasis and tumorigenesis. Int J Mol Sci. 2021;22(23):12850
There are 19 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases, Clinical Chemistry
Journal Section Research Article
Authors

Diler Us Altay 0000-0002-0465-8403

Serap Ozer Yaman 0000-0002-5089-0836

Sema Mısır 0000-0002-5919-3295

Project Number -
Submission Date April 15, 2025
Acceptance Date July 12, 2025
Publication Date December 22, 2025
Published in Issue Year 2025 Volume: 9 Issue: 3

Cite

APA Us Altay, D., Ozer Yaman, S., & Mısır, S. (2025). Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines. Ahi Evran Medical Journal, 9(3), 331-337. https://doi.org/10.46332/aemj.1676536
AMA Us Altay D, Ozer Yaman S, Mısır S. Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines. Ahi Evran Med J. December 2025;9(3):331-337. doi:10.46332/aemj.1676536
Chicago Us Altay, Diler, Serap Ozer Yaman, and Sema Mısır. “Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines”. Ahi Evran Medical Journal 9, no. 3 (December 2025): 331-37. https://doi.org/10.46332/aemj.1676536.
EndNote Us Altay D, Ozer Yaman S, Mısır S (December 1, 2025) Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines. Ahi Evran Medical Journal 9 3 331–337.
IEEE D. Us Altay, S. Ozer Yaman, and S. Mısır, “Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines”, Ahi Evran Med J, vol. 9, no. 3, pp. 331–337, 2025, doi: 10.46332/aemj.1676536.
ISNAD Us Altay, Diler et al. “Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines”. Ahi Evran Medical Journal 9/3 (December2025), 331-337. https://doi.org/10.46332/aemj.1676536.
JAMA Us Altay D, Ozer Yaman S, Mısır S. Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines. Ahi Evran Med J. 2025;9:331–337.
MLA Us Altay, Diler et al. “Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines”. Ahi Evran Medical Journal, vol. 9, no. 3, 2025, pp. 331-7, doi:10.46332/aemj.1676536.
Vancouver Us Altay D, Ozer Yaman S, Mısır S. Analysis of Mitotic Checkpoint Gene BUB3 Expression Levels in Raji and Jurkat Cell Lines. Ahi Evran Med J. 2025;9(3):331-7.

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