Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity

Background. Currently, little is known about the specific microRNAs involved in the development of cervical intraepithelial neoplasia (CIN1, 2, 3) and the transition to cancer in situ (CIS). Our meta-analysis allowed us to isolate 8 microRNAs (hsa-miR-1246, hsa-miR- 145-5p, hsa-miR-196b-5p, hsa-miR-...

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Main Authors: T. A. Dimitriadi, D. V. Burtsev, E. A. Dzhenkova, D. S. Kutilin
Format: Article
Language:Russian
Published: ABV-press 2020-09-01
Series:Успехи молекулярной онкологии
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Online Access:https://umo.abvpress.ru/jour/article/view/274
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author T. A. Dimitriadi
D. V. Burtsev
E. A. Dzhenkova
D. S. Kutilin
author_facet T. A. Dimitriadi
D. V. Burtsev
E. A. Dzhenkova
D. S. Kutilin
author_sort T. A. Dimitriadi
collection DOAJ
description Background. Currently, little is known about the specific microRNAs involved in the development of cervical intraepithelial neoplasia (CIN1, 2, 3) and the transition to cancer in situ (CIS). Our meta-analysis allowed us to isolate 8 microRNAs (hsa-miR-1246, hsa-miR- 145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p) with potential significance in the progression of precancerous diseases to cervical cancer. Objective: to analyze the expression features of hsa-miR-1246, hsa-miR-145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p and their target genes, as well as genes associated with them in common signaling pathways in the tissues of the cervix in patients with CIN1–3 and CIS. Materials and methods. To assess the expression level of microRNA and matrixRNA, the quantitative polymerase chain reaction in real time method was used. Data analysis was carried out in the Python programming language using the SciPy library. Search for target genes was performed using the TarPmiR algorithm and the overrepresentation of microRNAs in signaling pathways (Over-Representation Analysis) was analyzed. To identify genes associated with target genes in common signaling pathways, GIANT (Genome-scale Integrated Analysis of gene Networks in Tissues) and network integration with several associations algorithms were used. Results. For microRNAs miR-145, miR-196b, miR-34a, miR-20a, miR-21, miR-375 and miR-96 a decrease in expression was found in the subgroup of patients with CIS, while for 4 microRNAs (miR-145, miR-34a, miR-20a and miR-375), an increase in the expression level was found for CIN1, 2. The detected features of microRNA expression in subgroups of patients with CIN1–3 and CIS also affected the expression of their target genes (CDKN2A, MKI67, TOP2A and CD82), as well as the genes associated with them in common signaling pathways (PGK1, THBS4 (TSP4) and ECM1). Conclusion. Thus, the study revealed that each degree of CIN is characterized by its own specific molecular profile – the differential expression of microRNAs, their target genes and the genes associated with them in the general signaling pathways.
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spelling doaj-art-7fe239805fde4cebb6eae47b9c75e92a2025-08-20T04:00:14ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872020-09-0172476110.17650/2313-805X-2020-7-2-47-61186Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severityT. A. Dimitriadi0D. V. Burtsev1E. A. Dzhenkova2D. S. Kutilin3Regional Consultative and Diagnostic CenterRegional Consultative and Diagnostic CenterNational Medical Research Center for OncologyNational Medical Research Center for OncologyBackground. Currently, little is known about the specific microRNAs involved in the development of cervical intraepithelial neoplasia (CIN1, 2, 3) and the transition to cancer in situ (CIS). Our meta-analysis allowed us to isolate 8 microRNAs (hsa-miR-1246, hsa-miR- 145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p) with potential significance in the progression of precancerous diseases to cervical cancer. Objective: to analyze the expression features of hsa-miR-1246, hsa-miR-145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p and their target genes, as well as genes associated with them in common signaling pathways in the tissues of the cervix in patients with CIN1–3 and CIS. Materials and methods. To assess the expression level of microRNA and matrixRNA, the quantitative polymerase chain reaction in real time method was used. Data analysis was carried out in the Python programming language using the SciPy library. Search for target genes was performed using the TarPmiR algorithm and the overrepresentation of microRNAs in signaling pathways (Over-Representation Analysis) was analyzed. To identify genes associated with target genes in common signaling pathways, GIANT (Genome-scale Integrated Analysis of gene Networks in Tissues) and network integration with several associations algorithms were used. Results. For microRNAs miR-145, miR-196b, miR-34a, miR-20a, miR-21, miR-375 and miR-96 a decrease in expression was found in the subgroup of patients with CIS, while for 4 microRNAs (miR-145, miR-34a, miR-20a and miR-375), an increase in the expression level was found for CIN1, 2. The detected features of microRNA expression in subgroups of patients with CIN1–3 and CIS also affected the expression of their target genes (CDKN2A, MKI67, TOP2A and CD82), as well as the genes associated with them in common signaling pathways (PGK1, THBS4 (TSP4) and ECM1). Conclusion. Thus, the study revealed that each degree of CIN is characterized by its own specific molecular profile – the differential expression of microRNAs, their target genes and the genes associated with them in the general signaling pathways.https://umo.abvpress.ru/jour/article/view/274micrornagene expressioncervical intraepithelial neoplasiacervical cancer
spellingShingle T. A. Dimitriadi
D. V. Burtsev
E. A. Dzhenkova
D. S. Kutilin
Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity
Успехи молекулярной онкологии
microrna
gene expression
cervical intraepithelial neoplasia
cervical cancer
title Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity
title_full Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity
title_fullStr Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity
title_full_unstemmed Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity
title_short Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity
title_sort differential expression of micrornas and their target genes in cervical intraepithelial neoplasias of varying severity
topic microrna
gene expression
cervical intraepithelial neoplasia
cervical cancer
url https://umo.abvpress.ru/jour/article/view/274
work_keys_str_mv AT tadimitriadi differentialexpressionofmicrornasandtheirtargetgenesincervicalintraepithelialneoplasiasofvaryingseverity
AT dvburtsev differentialexpressionofmicrornasandtheirtargetgenesincervicalintraepithelialneoplasiasofvaryingseverity
AT eadzhenkova differentialexpressionofmicrornasandtheirtargetgenesincervicalintraepithelialneoplasiasofvaryingseverity
AT dskutilin differentialexpressionofmicrornasandtheirtargetgenesincervicalintraepithelialneoplasiasofvaryingseverity