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Involvement of methylation of group of miRNA genes in regulation of expression of RAR-beta2 and NKIRAS1 target genes in lung cancer
Year:
2012
Source of publication :
Molecular Biology
Authors :
Freedman, Moshe
;
.
Volume :
46
Co-Authors:
Khodyrev, D.S., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Pronina, I.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Rykov, S.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Beresneva, E.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Freedman, M.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Kazubskaya, T.P., Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russian Federation
Loginov, V.I., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Braga, E.A., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Facilitators :
From page:
693
To page:
704
(
Total pages:
12
)
Abstract:
To date, there are more than 2000 known human miRNAs, each of which may be involved in the regulation of hundreds of protein-coding target genes. In turn, the methylation of CpG islands affects the miRNA gene expression. Our aim was to evaluate the role of methylation in the regulation of miRNA gene expression and, consequently, in the regulation of the expression of target genes in primary lung tumors. Using a common collection of samples of non-small-cell lung cancer, we have performed a comprehensive study, including an analysis of the methylation status and level of expression of some miRNA genes and their potential target genes on chromosome 3, i. e., RAR-beta2 and NKIRAS1. The increased frequency of methylation in lung tumors compared to histologically normal tissue was revealed for miR-9-1 and miR-34b/c genes with significant statistics (P < 0. 05 by Fisher's exact test) and for miR-9-3 and miR-193a was marginally significant (P < 0. 1). A significant correlation was revealed between the changes in methylation and level of expression of miR-9-1 gene (P ≈ 5 × 10 -12 by Spearman) in lung tumors, which suggests the role of methylation in the regulation of expression of these miRNA genes. Furthermore, a statistically significant negative correlation (P ≈ 3 × 10 -12 to 5 × 10 -13 by Spearman) was found between changes in the levels of expression of miR-9-1 and miR-17 and RAR-beta2 target genes, as well as between the changes in the level of expression of miR-17 and NKIRAS1 that were not previously analyzed. The inverse relationship between the levels of expression of miRNA genes and their target genes is consistent with the known mechanism of the suppression of the expression of protein-coding genes under the action of miRNA. For the first time, significant correlations (P ≈ 3 × 10 -10 to 4 × 10 -13 by Spearman) were shown between changes in the methylation status of miRNA genes (miR-9-1, miR-9-3, miR-34b/c, miR-193a) and the level of expression of the RAR-beta2 target gene and changes in the methylation status of miR-34b/c, and miR-193a and the level of expression of the NKIRAS1 target gene in the primary lung tumors, which suggests the possibility of indirect effects of the methylation of miRNA genes on the level of expression of target genes. © 2012 Pleiades Publishing, Ltd.
Note:
Related Files :
level of expression
Methylation
methylation-specific PCR
miRNA genes
mRNA
pri-miRNA
Show More
Related Content
More details
DOI :
10.1134/S002689331205007X
Article number:
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
30086
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:51
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Scientific Publication
Involvement of methylation of group of miRNA genes in regulation of expression of RAR-beta2 and NKIRAS1 target genes in lung cancer
46
Khodyrev, D.S., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Pronina, I.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Rykov, S.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Beresneva, E.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Freedman, M.V., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Kazubskaya, T.P., Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russian Federation
Loginov, V.I., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Braga, E.A., State Research Center GosNIIgenetika, Moscow 117545, Russian Federation
Involvement of methylation of group of miRNA genes in regulation of expression of RAR-beta2 and NKIRAS1 target genes in lung cancer
To date, there are more than 2000 known human miRNAs, each of which may be involved in the regulation of hundreds of protein-coding target genes. In turn, the methylation of CpG islands affects the miRNA gene expression. Our aim was to evaluate the role of methylation in the regulation of miRNA gene expression and, consequently, in the regulation of the expression of target genes in primary lung tumors. Using a common collection of samples of non-small-cell lung cancer, we have performed a comprehensive study, including an analysis of the methylation status and level of expression of some miRNA genes and their potential target genes on chromosome 3, i. e., RAR-beta2 and NKIRAS1. The increased frequency of methylation in lung tumors compared to histologically normal tissue was revealed for miR-9-1 and miR-34b/c genes with significant statistics (P < 0. 05 by Fisher's exact test) and for miR-9-3 and miR-193a was marginally significant (P < 0. 1). A significant correlation was revealed between the changes in methylation and level of expression of miR-9-1 gene (P ≈ 5 × 10 -12 by Spearman) in lung tumors, which suggests the role of methylation in the regulation of expression of these miRNA genes. Furthermore, a statistically significant negative correlation (P ≈ 3 × 10 -12 to 5 × 10 -13 by Spearman) was found between changes in the levels of expression of miR-9-1 and miR-17 and RAR-beta2 target genes, as well as between the changes in the level of expression of miR-17 and NKIRAS1 that were not previously analyzed. The inverse relationship between the levels of expression of miRNA genes and their target genes is consistent with the known mechanism of the suppression of the expression of protein-coding genes under the action of miRNA. For the first time, significant correlations (P ≈ 3 × 10 -10 to 4 × 10 -13 by Spearman) were shown between changes in the methylation status of miRNA genes (miR-9-1, miR-9-3, miR-34b/c, miR-193a) and the level of expression of the RAR-beta2 target gene and changes in the methylation status of miR-34b/c, and miR-193a and the level of expression of the NKIRAS1 target gene in the primary lung tumors, which suggests the possibility of indirect effects of the methylation of miRNA genes on the level of expression of target genes. © 2012 Pleiades Publishing, Ltd.
Scientific Publication
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