Email this article Hypermethylation of the microRNA miR-124, miR-125b, miR-127, and miR-129 in ovarian carcinoma is involved in suppression of their expression and associated with both the development and progression of ovarian cancer
- Authors: Braga E.A.1,2, Pronina I.V.1, Utkin D.O.3, Filippova E.A.1, Burdennyy A.M.1, Loginov V.I.4, Fridman M.V.5, Kazubskaya T.P.6, Kushlinskii N.E.6
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Affiliations:
- Institute of General Pathology and Pathophysiology
- Medical Genetic Science Center
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
- Institute of General Pathology and Pathophysiology Medical Genetic Science Center
- Vavilov Institute of General Genetics
- N.N. Blokhin National Medical Research Centre of Oncology
- Issue: Vol 47, No 1 (2019)
- Pages: 47-53
- Section: ARTICLES
- URL: https://almclinmed.ru/jour/article/view/962
- DOI: https://doi.org/10.18786/2072-0505-2019-47-003
- ID: 962
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Abstract
Rationale: We have previously identified a group of microRNA genes (MIR-107, MIR-1258, MIR-130b, MIR-34b/c, MIR-9-1, MIR-9-3 et al.), whose methylation was involved into the development and progression of ovarian cancer. Aim: To expand the range of microRNA genes hypermethylated in ovarian cancer and to study the role of this modification in the pathogenesis and progression of ovarian cancer. Materials and methods: The study was performed on a series of 76 ovarian cancer and 13 peritoneal metastases samples. The method of bisulfite DNA conversion followed by methylation-specific polymerase chain reaction (PCR) was used to assess the methylation status of the microRNA genes; the expression of these genes was measured by quantitative real-time PCR. Results: Compared to histologically unchanged ovarian tissue, there was a significant increase in methylation frequencies in the tumor samples for 6 microRNA genes studied: MIR-124-1, MIR-124-2, MIR-124-3, MIR-125B-1, MIR-127, and MIR-129-2 (p ≤ 10-3). The expression level of 4 microRNAs (miR-124-3p, miR-125b-5p, miR-127-5p, miR-129-5p) encoded by these genes was suppressed, with a significant correlation between changes in their expression levels and the gene methylation (rs = 0.63–0.94, p ≤ 10-4). In addition, there were statistically significant associations between methylation of 5 genes (MIR-124-2, MIR-124-3, MIR-125B-1, MIR-127, and MIR-129-2) and the parameters of cancer progression, such as its clinical stage, metastatic spread, tumor size and invasion, and to a lesser extent with a decrease in the differentiation grade. The association of 5 microRNA genes with metastatic spread was confirmed by the analysis of peritoneal macro-metastases from 13 patients. Conclusion: We have demonstrated the functional significance of aberrant methylation in a group of microRNA genes for suppression of their expression in ovarian carcinomas. There is an association of microRNA gene hypermethylation with the progression of ovarian cancer, including metastatic spread to the peritoneum.
About the authors
E. A. Braga
Institute of General Pathology and Pathophysiology;Medical Genetic Science Center
Author for correspondence.
Email: eleonora10_45@mail.ru
PhD, Doctor of Biol. Sci., Professor, Chief Research Fellow, Head of the Laboratory of Pathogenomics and Transcriptomics;
Leading Research Fellow, Laboratory of Molecular Genetics of Complicated Inherited Diseases
8 Baltiyskaya ul., Moscow, 125315, Russian Federation
+7 (917) 545 43 93.
Russian FederationI. V. Pronina
Institute of General Pathology and Pathophysiology
Email: fake@neicon.ru
PhD (in Biol.), Research Fellow, Laboratory of Pathogenomics and Transcriptomics
8 Baltiyskaya ul., Moscow, 125315, Russian Federation
Russian FederationD. O. Utkin
A.I. Yevdokimov Moscow State University of Medicine and Dentistry
Email: fake@neicon.ru
MD, Surgeon, Applicant, Chair of Clinical Biochemistry and Laboratory Diagnostics, Faculty of Postgraduate Education
20–1 Delegatskaya ul., Moscow, 127473, Russian Federation
Russian FederationE. A. Filippova
Institute of General Pathology and Pathophysiology
Email: fake@neicon.ru
Postgraduate Student, Junior Research Fellow, Laboratory of Pathogenomics and Transcriptomics
8 Baltiyskaya ul., Moscow, 125315, Russian Federation
Russian FederationA. M. Burdennyy
Institute of General Pathology and Pathophysiology
Email: fake@neicon.ru
PhD (in Biol.), Leading Research Fellow, Laboratory of Pathogenomics and Transcriptomics
8 Baltiyskaya ul., Moscow, 125315, Russian Federation
Russian Federation
V. I. Loginov
Institute of General Pathology and PathophysiologyMedical Genetic Science Center
Email: fake@neicon.ru
PhD (in Biol.), Leading Research Fellow, Laboratory of Pathogenomics and Transcriptomics; Senior Research Fellow, Laboratory of Molecular Genetics of Complicated Inherited Diseases
8 Baltiyskaya ul., Moscow, 125315, Russian Federation
1 Moskvorech'e ul., Moscow, 115522, Russian Federation
Russian FederationM. V. Fridman
Vavilov Institute of General Genetics
Email: fake@neicon.ru
PhD (in Biol.), Research Fellow, Laboratory of Systems Biology and Computational Genetics
3 Gubkina ul., Moscow, 119333, Russian Federation
Russian FederationT. P. Kazubskaya
N.N. Blokhin National Medical Research Centre of Oncology
Email: fake@neicon.ru
MD, PhD, Oncogenetic Physician, Senior Research Fellow, Laboratory of Clinical Oncogenetics
24 Kashirskoe shosse, Moscow, 115478, Russian Federation
Russian FederationN. E. Kushlinskii
N.N. Blokhin National Medical Research Centre of Oncology
Email: fake@neicon.ru
MD, PhD, Professor, Member-Correspondent of Russian Academy of Sciences, Head of Clinical Biochemistry Laboratory
24 Kashirskoe shosse, Moscow, 115478, Russian Federation
Russian FederationReferences
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