{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:14:00Z","timestamp":1789427640706,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-25-00222"],"award-info":[{"award-number":["22-25-00222"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The regulation of oncogenes by microRNA is a focus of medical research. hsa-miR-203, hsa-mir-129, hsa-miR-34a, hsa-miR-34b and hsa-miR-34c are oncosuppressive microRNAs that mediate the antitumor activity of p53. We seek to evaluate the frequencies, co-occurrence and clinical significance of the methylation of the MIR-203, MIR-129-2, MIR-34A and MIR-34B\/C genes in the tumor tissue of diffuse large B-cell lymphoma (DLBCL). The methylation was assessed in 73 samples of DLBCL and in 11 samples of lymph nodes of reactive follicular hyperplasia by Methyl-Specific Polymerase Chain Reaction (MS-PCR) and Methylation-Sensitive High-Resolution-Melting (MS-HRM) methods. All four studied genes were not methylated in the tissue of reactive lymphatic nodes. The methylation frequencies of the MIR-129-2, MIR-203, MIR-34A and MIR-34B\/C genes in lymphoma tissue were 67%, 66%, 27% and 62%, respectively. Co-occurrence of MIR-203, MIR-129-2 and MIR-34B\/C genes methylation, as well as the methylation of MIR-34B\/C and MIR-34A pair genes were detected. The MIR-34A gene methylation was associated with increased International Prognostic Index (IPI) (p = 0.002), whereas the MIR-34B\/C (p = 0.026) and MIR-203 (p = 0.011) genes\u2019 methylation was connected with Ki-67 expression level in tumor tissue at more than 45%. We found an increasing frequency of detection of MIR-34A gene methylation in the group of patients with the Germinal-Center B-cell like (GCB-like) subtype of DLBCL (p = 0.046). There was a trend towards a decrease in the remission frequency after the first line of therapy (p = 0.060) and deterioration in overall survival (OS) (p = 0.162) in patients with DLBCL with methylation of the MIR-34A promoter. The methylation of the MIR-34A, MIR-34B\/C, MIR-129-2 and MIR-203 genes in DLBCL is tumor-specific and occurs in combination. The methylation of the studied genes may be a potential differential diagnostic biomarker to distinguish between lymphoma and reactive lymph nodes, while its independent predictive value has not been confirmed yet.<\/jats:p>","DOI":"10.3390\/genes13081401","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Methylation of the p53 Targets the Genes MIR-203, MIR-129-2, MIR-34A and MIR-34B\/C in the Tumor Tissue of Diffuse Large B-Cell Lymphoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-7285","authenticated-orcid":false,"given":"Elena N.","family":"Voropaeva","sequence":"first","affiliation":[{"name":"Research Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630089 Novosibirsk, Russia"},{"name":"Faculty of Advanced Training and Retraining of Doctors, Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana I.","family":"Pospelova","sequence":"additional","affiliation":[{"name":"Faculty of Advanced Training and Retraining of Doctors, Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-1609","authenticated-orcid":false,"given":"Yuriy L.","family":"Orlov","sequence":"additional","affiliation":[{"name":"Research Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630089 Novosibirsk, Russia"},{"name":"The Digital Health Institute, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Churkina","sequence":"additional","affiliation":[{"name":"Faculty of Advanced Training and Retraining of Doctors, Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Berezina","sequence":"additional","affiliation":[{"name":"Faculty of Advanced Training and Retraining of Doctors, Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A.","family":"Gurazheva","sequence":"additional","affiliation":[{"name":"Research Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630089 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana A.","family":"Ageeva","sequence":"additional","affiliation":[{"name":"Faculty of Advanced Training and Retraining of Doctors, Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, 630091 Novosibirsk, Russia"},{"name":"Regional Center of High Medical Technologies, 630084 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga B.","family":"Seregina","sequence":"additional","affiliation":[{"name":"Faculty of Advanced Training and Retraining of Doctors, Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir N.","family":"Maksimov","sequence":"additional","affiliation":[{"name":"Research Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630089 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Syeda, A.Z., Langden, S.S.S., Munkhzul, C., Lee, M., and Song, S.J. 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