Kovalenko Tatyana F, Morozova Ksenia V, Pavlyukov Marat S, Anufrieva Ksenia S, Bobrov Mikhail Yu, Gamisoniya Alina M, Ozolinya Lyudmila A, Dobrokhotova Yulia E, Shakhparonov Mikhail I, Patrushev Lev I
Laboratory of membrane bioenergetics, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Moscow, Russia.
Department of Obstetrics and Gynecology, Pirogov Russian National Research Medical University, Moscow, Russia.
PLoS One. 2021 Jan 22;16(1):e0243093. doi: 10.1371/journal.pone.0243093. eCollection 2021.
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.
经过加工的假基因PTENP1参与PTEN表达的调控，并在多种恶性肿瘤中发挥肿瘤抑制作用。在我们之前的研究中，我们发现PTENP1甲基化不仅存在于肿瘤组织中，在45岁以上女性的正常子宫内膜组织中也存在。在此，我们使用甲基化特异性PCR分析了从236名不同年龄组女性收集的恶性和非恶性子宫内膜组织中PTENP1启动子区域附近CpG岛的甲基化状态。为了证实我们的结果，我们还分析了来自TCGA数据库的431名子宫内膜癌女性的RNA测序和微阵列数据。我们证明，老年患者中PTENP1的甲基化显著增加。我们还发现子宫内膜组织中PTENP1表达水平随年龄增长而增加。根据我们的数据，PTENP1甲基化提高了假基因正义转录本的水平。反过来，这种转录本的高水平与子宫内膜癌更有利的预后相关。获得的数据表明，PTENP1甲基化与正常和增生性子宫内膜组织中与年龄相关的变化有关。我们推测，PTENP1甲基化随年龄增长而增加以及随后其表达的升高可能是一种保护机制，旨在防止围绝经期、绝经和绝经后女性子宫内膜组织发生恶性转化。
