Changes in the MIR-143
https://doi.org/10.18699/SSMJ20230519
Abstract
The study of DNA methylation status in malignant lymphomas is a new field of research in oncohematology. The aim of this study was to quantify the level of methylation of the MIR-143 gene in the tumor tissue of patients with diffuse large B-cell lymphoma (DLBCL). Material and methods. The study included 81 tumor samples of DLBCL (26 of germinal and 55 of non-germinal origin) and 11 biopsies of reactive lymph nodes. To quantify the methylation of the MIR-143 gene, the method of direct bisulfite sequencing by Sanger was used with the calculation of the average level of methylation of the analyzed CpG-sites. Results. The average level of MIR-143 methylation in tumor samples was significantly lower than the values in reactive lymph nodes (64.43 ± 19.92 и 76.27 ± 4.92 %, respectively, p = 0.049), did not depend on the immunohistochemical subtype of the tumor and showed a greater spread of values. In the lymphoma samples, there was predominant hypomethylation of one of the four analyzed CpG-dinucleotides within the boundaries of the analyzed fragment. Conclusion. The data on a change in the pattern of the MIR-143 gene methylation in the tumor tissue of DLBCL were obtained. To establish the role of microRNA in the pathogenesis of DLBCL further studies aimed at clarifying the mechanisms of epigenetic regulation of MIR-143 expression in lymphoma cells and identification of this microRNA targets are required.
Supporting agencies: This work was supported by Russian scientific fund, grant № 22-25-00222.
About the Authors
E. N. Voropaeva
Research Institute of Internal and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
doctor of medical sciences
630089, Novosibirsk, Borisa Bogatkova st., 175/1
630091, Novosibirsk, Krasny ave., 52
T. I. Pospelova
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
doctor of medical sciences, professor
630091, Novosibirsk, Krasny ave., 52
A. M. Nesterets
Research Institute of Internal and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS
Russian Federation
Russian Federation
candidate of medical sciences
630089, Novosibirsk, Borisa Bogatkova st., 175/1
M. I. Churkina
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
630091, Novosibirsk, Krasny ave., 52
O. V. Berezina
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
candidate of medical sciences
630091, Novosibirsk, Krasny ave., 52
V. N. Maksimov
Research Institute of Internal and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
doctor of medical sciences, professor
630089, Novosibirsk, Borisa Bogatkova st., 175/1
630091, Novosibirsk, Krasny ave., 52
References
1. Kabanov I.N., Tishchenko L.I. Changing the DNA methylation of repetitive sequences and single-copy genes in cancer and other human diseases. Vestnik Sankt-Peterburgskogo universiteta = Bulletin of Saint-Petersburg University. 2014;3(3):62–83. [In Russian].
2. Loginov V.I., Burdennyy A.M., Pronina I.V., Filippova E.A., Kazubskaya T.P., Braga E.A. The role of promoter DNA methylation of six cancer-associated miRNA genes in ovarian cancer development and progression. Biotecnol. Apl. 2016;33(3):3211–3215.
3. Piletič K., Kunej T. MicroRNA epigenetic signatures in human disease. Arch. Toxicol. 2016;90(10):2405–2419. doi: 10.1007/s00204-0161815-7
4. Voropaeva E.N., Pospelova T.I., Berezina O.V., Churkina M.I., Gurazheva A.A., Maksimov V.N. Methylation of p53-responsive oncosuppressive microRNA genes in hemoblastosis. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology. 2022;21(2):130– 142. [In Russian]. doi: 10.21294/1814-4861-2022-212-130-142
5. Voropaeva E.N., Pospelova T.I., Orlov Y.L., Churkina M.I., Berezina O.V., Gurazheva A.A., Ageeva T.A., Seregina O.B., Maksimov V.N. The methylation of the p53 targets the genes MIR-203, MIR-129-2, MIR34A and MIR-34B/C in the tumor tissue of diffuse large B-cell lymphoma. Genes (Basel). 2022;13(8):1401. doi: 10.3390/genes13081401
6. Voropaeva E.N., Pospelova T.I., Churkina M.I., Gurazheva A.A., Voevoda M.I., Maximov V.N. Complex analysis of p53-responsive microRNA genes methylation and TР53 gene mutations in diffuse large B-cell lymphoma. Meditsinskaya genetika = Medical Genetics. 2022;21(11):62–66. [In Russian]. doi: 10.25557/2073-7998.2022.11.62-66
7. Akao Y., Nakagawa Y., Kitade Y., Kinoshita T., Naoe T. 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., Hoefig K.P., Repsilber D., Thorns C., Ziepert M., Wesche K.O., Thiere M., Loeffler M., Klapper W., Pfreundschuh M., … Feller A.C. MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas. Br. J. Haematol. 2008;142(5):732–744. doi: 10.1111/j.13652141.2008.07237.x
9. Chen W., Lang Z., Ren C., Yang P., Zhang B. MiR-143 acts as a novel Big mitogen activated protein kinase 1 suppressor and may inhibit invasion of glioma. Oncol. Rep. 2019;42(3):1194–1204. doi: 10.3892/or.2019.7218
10. Dou L., Zheng D., Li J., Li Y., Gao L., Wang L., Yu L. Methylation-mediated repression of microRNA-143 enhances MLL-AF4 oncogene expression. Oncogene. 2012;31(4):507–517. doi: 10.1038/onc.2011.248
11. Jiang M., Zhang Y., Fei J., Chang X., Fan W., Qian X., Zhang T., Lu D. Rapid quantification of DNA methylation by measuring relative peak heights in direct bisulfite-PCR sequencing traces. Lab. Invest. 2010;90(2):282–290. doi: 10.1038/labinvest.2009.132
12. Drosou V., Kapazoglou A., Letsiou S., Tsaftaris A.S., Argiriou A. 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
13. Grunau C., Clark S.J., Rosenthal A. Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res. 2001;29(13):E65–5. doi: 10.1093/nar/29.13.e65
14. Lawrie C.H., Chi J., Taylor S., Tramonti D., Ballabio E., Palazzo S., Saunders N.J., Pezzella F., Boultwood J., Wainscoat J.S., Hatton C.S.R. Expression of microRNAs in diffuse 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.15824934.2008.00628.x
15. 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 Research. 2014;42(12):7528–7538. doi: 10.1093/nar/gku461
16. Song Y., van den Berg P.R., Markoulaki S., Soldner F., Dall’Agnese A., Henninger J.E., Drotar J., Rosenau N., Cohen M.A., Young R.A., … Jaenisch R. Dynamic enhancer DNA methylation as basis for transcriptional and cellular heterogeneity of ESCs. Mol. Cell. 2019;75(5):905–920.e6. doi: 10.1016/j.molcel.2019.06.045
17. Lozada-Delgado E.L., Grafals-Ruiz N., Miranda-Román M.A., Santana-Rivera Y., Valiyeva F., Rivera-Díaz M., Marcos-Martínez M.J., Vivas-Mejía P.E. Targeting MicroRNA-143 leads to inhibition of glioblastoma tumor progression. Cancers (Basel). 2018;10(10):382. doi: 10.3390/cancers10100382
18. Yoon S., Choi E.H., Park S.J., Kim K.P. α-Kleisin subunit of cohesin preserves the genome integrity of embryonic stem cells. BMB Rep. 2023;56(2):108–113. doi: 10.5483/BMBRep.2022-0106
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