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Methylation of the PTENP1 pseudogene as potential epigenetic marker of age-related changes in human endometrium
Author(s) -
Т. Ф. Коваленко,
K. V. Morozova,
Marat S. Pavlyukov,
Ksenia S. Anufrieva,
M. Yu. Bobrov,
Alina M. Gamisoniya,
Lyudmila A. Ozolinya,
Dobrokhotova Yu.E. Dobrokhotova,
M. I. Shakhparonov,
Lev I. Patrushev
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0243093
Subject(s) - methylation , biology , pseudogene , dna methylation , endometrium , epigenetics , endometrial cancer , malignant transformation , cancer research , cancer , gene , gene expression , genetics , endocrinology , genome
The processed pseudogene PTENP1 is involved in the regulation of the expression of the PTEN and acts as a tumor suppressor in many types of malignances. In our previous study we showed that PTENP1 methylation is present not only in tumor, but also in normal endometrium tissues of women over 45 years old. Here we used methylation-specific PCR to analyze methylation status of CpG island located near promoter region of PTENP1 in malignant and non-malignant endometrium tissues collected from 236 women of different age groups. To confirm our results, we also analyzed RNA sequencing and microarray data from 431 women with endometrial cancer from TCGA database. We demonstrated that methylation of PTENP1 is significantly increased in older patients. We also found an age-dependent increase in the level of PTENP1 expression in endometrial tissue. According to our data, PTENP1 methylation elevates the level of the pseudogene sense transcript. In turn, a high level of this transcript correlates with a more favorable prognosis in endometrial cancer. The data obtained suggested that PTENP1 methylation is associated with age-related changes in normal and hyperplastic endometrial tissues. We assumed that age-related increase in PTENP1 methylation and subsequent elevation of its expression may serve as a protective mechanism aimed to prevent malignant transformation of endometrial tissue in women during the perimenopause, menopause, and postmenopause periods.

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