Preview

Journal of Siberian Medical Sciences

Advanced search

Evaluation of MIR-143 and MIR-145 genes methylation in lymph nodes of patients with diff use large B-cell lymphoma

https://doi.org/10.31549/2542-1174-2023-7-3-94-108

Abstract

I n t r o d u c t i o n . The expression of miR-143 and miR-145 oncosuppressive microRNAs is observed in all types of normal tissues studied and, according to numerous studies, it is lost in malignant neoplasms. A decrease in the expression of these microRNAs in diff use large B-cell lymphoma (DLBCL) is described, the mechanisms of which require additional study. A i m . To evaluate the methylation of MIR-143 and MIR-145 genes in the lymph node tissue of patients with DLBCL and lymph nodes of patients with reactive follicular hyperplasia.

M a t e r i a l s a n d m e t h o d s . The study included biopsies of 14 formalin-fi xed and paraffi nized tumor lymph nodes of patients with DLBCL and 11 lymph nodes of patients with reactive lymphadenopathy. The methylation status of the MIR-145 gene in samples was determined by the method of methyl-specifi c polymerase chain reaction. Direct bisulfi te sequencing based on the Sanger method was used to quantify the methylation of the MIR-143 gene.

R e s u l t s . It was found that all the studied samples, both reactive and tumor, had methylation of the MIR-145 gene. A similar level of methylation of CpG dinucleotides of the MIR-143 gene was registered in all samples of reactive lymph node tissue, whereas tumor samples showed greater heterogeneity. In the samples of DLBCL, namely a non-germinal B cell phenotype, the average level of methylation of the studied fragment of the MIR-143 gene sequence was signifi cantly lower, than in the samples of reactive lymph nodes (p = 0.026).

C o n c l u s i o n . The methylation of MIR-143 and MIR-145 genes detected in the lymph nodes of patients with DLBCL is not tumor-specifi c. The complex cellular composition of the analyzed samples, as well as the diff erent density of microvessels, may explain the diff erences in the level of MIR-143 methylation in the tissue of reactive and tumor lymph nodes.

About the Authors

E. N. Voropaeva
Research Institute of Internal and Preventive Medicine, Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Elena N. Voropaeva – Dr. Sci. (Med.), Leading Researcher, Laboratory of Molecular and Genetic Studies of Internal Diseases; Associate Professor

Novosibirsk



T. I. Pospelova
Novosibirsk State Medical University
Russian Federation

Tatyana I. Pospelova – Dr. Sci. (Med.), Professor, Head, Department of Therapy, Hematology and Transfusiology

Novosibirsk



M. I. Churkina
Novosibirsk State Medical University
Russian Federation

Maria I. Churkina – Postgraduate Student, Department of Therapy, Hematology and Transfusiology

Novosibirsk



A. M. Nesterets
Research Institute of Internal and Preventive Medicine, Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Alina M. Nesterets – Junior Researcher, Laboratory of Genetic and Environmental Determinants of the Human Life Cycle

Novosibirsk



O. V. Berezina
Novosibirsk State Medical University
Russian Federation

Olga V. Berezina – Cand. Sci. (Med.), Assistant, Department of Therapy, Hematology and Transfusiology

Novosibirsk



N. V. Skvortsova
Novosibirsk State Medical University
Russian Federation

Nataliya V. Skvortsova – Dr. Sci. (Med.), Associate Professor, Department of Therapy, Hematology and Transfusiology

Novosibirsk



T. A. Ageeva
Novosibirsk State Medical University
Russian Federation

Tatyana A. Ageeva – Dr. Sci. (Med.), Professor, Department of Pathological Anatomy

Novosibirsk



V. N. Maksimov
Research Institute of Internal and Preventive Medicine, Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Vladimir N. Maksimov – Dr. Sci. (Med.), Professor, Head, Laboratory of Molecular Genetic Studies of Internal Diseases; Associate Professor

Novosibirsk



References

1. Kent O.A., McCall M.N., Cornish T.C., Halushka M.K. Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res. 2014;42(12):7528–7538. DOI: 10.1093/nar/gku461.

2. Pidíkova P., Reis R., Herichova I. miRNA clusters with down-regulated expression in human colorectal cancer and their regulation. Int. J. Mol. Sci. 2020;21(13):4633. DOI: 10.3390/ijms21134633.

3. Lonsdale J., Thomas J., Salvatore M. et al. The Genotype- Tissue Expression (GTEx) project. Nat. Genet. 2013;45(6):580-585. DOI: 10.1038/ng.2653.

4. Fischer L., Hummel M., Korfel A. et al. Diff erential micro-RNA expression in primary CNS and nodal diff use large B-cell lymphomas. Neuro-Oncology. 2011;13(10):1090-1098. DOI: 10.1093/neuonc/nor107.

5. Zhang Y., Wang Z., Chen M. et al. MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer. Mol. Cancer. 2012;11:23. DOI: 10.1186/1476-4598-11-23.

6. Takagi T., Iio A., Nakagawa Y. et al. Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology. 2009;77(1):12-21. DOI: 10.1159/000218166.

7. Akao Y., Nakagawa Y., Kitade Y. et al. Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci. 2007;98(12):1914-1920. DOI: 10.1111/j.1349-7006.2007.00618.x.

8. Roehle A., Hoefi g K.P., Repsilber D. et al. MicroRNA signatures characterize diff use large B-cell lymphomas and follicular lymphomas. Br. J. Haematol. 2008;142(5):732-744. DOI: 10.1111/j.1365-2141.2008.07237.x.

9. Voropaeva E.N., Pospelova T.I., Orlov Y.L. et al. The methylation of the p53 targets the genes MIR- 203, MIR-129-2, MIR-34A and MIR-34B/C in the tumor tissue of diff use large B-cell lymphoma. Genes. 2022;13:1401. DOI: 10.3390/genes13081401.

10. Voropaeva E.N., Pospelova T.I., Churkina M.I. et al. Complex analysis of p53-responsive microRNA genes methylation and TР53 gene mutations in Diff use Large B-cell Lymphoma. Medical Genetics. 2022;21(11):62- 66. DOI: 10.25557/2073-7998.2022.11.62-66. (In Russ.)

11. GeneCaRNA. The Human ncRNA Database. MIR143 Gene – MicroRNA 143. URL: https://www.genecards. org/cgi-bin/carddisp.pl?gene=MIR143 (accessed 22.04.2023).

12. GeneCaRNA. The Human ncRNA Database. MIR145 Gene – MicroRNA 145. URL: https://www.genecards.org/cgi-bin/carddisp. pl?gene=MIR145&keywords=mir-145 (accessed 22.04.2023).

13. Suh S.O., Chen Y., Zaman M.S. et al. MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. Carcinogenesis. 2011;32(5):772- 778. DOI: 10.1093/carcin/bgr036.

14. Jiang M., Zhang Y., Fei J. et al. Rapid quantifi cation of DNA methylation by measuring relative peak heights in direct bisulfi te-PCR sequencing traces. Lab. Invest. 2010;90(2):282-290. DOI: 10.1038/labinvest.2009.132.

15. Dou L., Zheng D., Li J. et al. Methylation-mediated repression of microRNA-143 enhances MLL-AF4 oncogene expression. Oncogene. 2012;31(4):507-517. DOI: 10.1038/onc.2011.248.

16. Drosou V., Kapazoglou A., Letsiou S. et al. Drought induces variation in the DNA methylation status of the barley HvDME promoter. J. Plant Res. 2021;134(6):1351-1362. DOI: 10.1007/s10265-021-01342-z.

17. Grunau C., Clark S.J., Rosenthal A. Bisulfi te genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res. 2001;29(13):E65. DOI: 10.1093/nar/29.13.e65.

18. Voropaeva E.N., Pospelova T.I., Berezina O.V. et al. Methylation of p53-responsive oncosuppressive microRNA genes in hemoblastosis. Siberian Journal of Oncology. 2022;21(2):130-142. DOI: 10.21294/1814-4861-2022-21-2-130-142. (In Russ.)

19. Volkova N.S., Ermakov A.S. (2017). DNA methylation and regulation of gene expression. XXI Tsarskoye Selo R eadings: Proceedings of the International Scientifi c Conference April 25–26, 2017. St. Petersburg, Vol. 3, pp. 285–288. (In Russ.)

20. Lawrie C.H., Chi J., Taylor S. et al. Expression of microRNAs in diff use large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma. J. Cell. Mol. Med. 2009;13(7):1248-1260. DOI: 10.1111/j.1582-4934.2008.00628.x.

21. Marinaccio C., Ingravallo G., Gaudio F. et al. Microvascular density, CD68 and tryptase expression in human diff use large B-cell lymphoma. Leuk. Res. 2014;38(11):1374-1377. DOI: 10.1016/j.leukres. 2014.09.007.

22. Marinaccio C., Ingravallo G., Gaudio F. et al. T cells, mast cells and microvascular density in diff use large B cell lymphoma. Clin. Exp. Med. 2016;16(3):301-306. DOI: 10.1007/s10238-015-0354-5.

23. Abdou A.G., Asaad N., Kandil M. et al. Signifi cance of stromal-1 and stromal-2 signatures and biologic prognostic model in diff use large B-cell lymphoma. Cancer Biol. Med. 2017;14(2):151-161. DOI: 10.20892/j.issn.2095-3941.2017.0007.

24. Guidolin D., Tamma R., Annese T. et al. Diff erent spatial distribution of infl ammatory cells in the tumor microenvironment of ABC and GBC subgroups of diff use large B cell lymphoma. Clin. Exp. Med. 2021;21(4):573-578. DOI: 10.1007/s10238-021-00716-w.


Review

For citations:


Voropaeva E.N., Pospelova T.I., Churkina M.I., Nesterets A.M., Berezina O.V., Skvortsova N.V., Ageeva T.A., Maksimov V.N. Evaluation of MIR-143 and MIR-145 genes methylation in lymph nodes of patients with diff use large B-cell lymphoma. Journal of Siberian Medical Sciences. 2023;(3):94-108. (In Russ.) https://doi.org/10.31549/2542-1174-2023-7-3-94-108

Views: 84


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2542-1174 (Print)