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子宫内膜异位症与在位内膜中hTERC显著增加及端粒/端粒酶相关基因改变有关:一项体外和计算机模拟研究

Endometriosis Is Associated with a Significant Increase in hTERC and Altered Telomere/Telomerase Associated Genes in the Eutopic Endometrium, an Ex-Vivo and In Silico Study.

作者信息

Alnafakh Rafah, Choi Fiona, Bradfield Alice, Adishesh Meera, Saretzki Gabriele, Hapangama Dharani K

机构信息

Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool L8 7SS, UK.

Department of Pathology, Al-Hilla Teaching Hospital, Babil 51001, Iraq.

出版信息

Biomedicines. 2020 Dec 9;8(12):588. doi: 10.3390/biomedicines8120588.

Abstract

Telomeres protect chromosomal ends and they are maintained by the specialised enzyme, telomerase. Endometriosis is a common gynaecological disease and high telomerase activity and higher hTERT levels associated with longer endometrial telomere lengths are characteristics of eutopic secretory endometrial aberrations of women with endometriosis. Our ex-vivo study examined the levels of hTERC and DKC1 RNA and dyskerin protein levels in the endometrium from healthy women and those with endometriosis ( = 117). The in silico study examined endometriosis-specific telomere- and telomerase-associated gene (TTAG) transcriptional aberrations of secretory phase eutopic endometrium utilising publicly available microarray datasets. Eutopic secretory endometrial hTERC levels were significantly increased in women with endometriosis compared to healthy endometrium, yet dyskerin mRNA and protein levels were unperturbed. Our in silico study identified 10 TTAGs ( and ) to be altered in mid-secretory endometrium of women with endometriosis. High levels of hTERC and the identified other TTAGs might be part of the established alteration in the eutopic endometrial telomerase biology in women with endometriosis in the secretory phase of the endometrium and our data informs future research to unravel the fundamental involvement of telomerase in the pathogenesis of endometriosis.

摘要

端粒保护染色体末端,由特殊的端粒酶维持。子宫内膜异位症是一种常见的妇科疾病,子宫内膜异位症患者在位分泌期子宫内膜异常的特征是端粒酶活性高以及与人端粒酶逆转录酶(hTERT)水平较高相关的子宫内膜端粒长度更长。我们的体外研究检测了健康女性和子宫内膜异位症患者(n = 117)子宫内膜中hTERC和DKC1 RNA水平以及盘状结构域结合蛋白水平。计算机模拟研究利用公开可用的微阵列数据集检测了分泌期在位子宫内膜的子宫内膜异位症特异性端粒和端粒酶相关基因(TTAG)转录异常。与健康子宫内膜相比,子宫内膜异位症患者在位分泌期子宫内膜的hTERC水平显著升高,但盘状结构域结合蛋白的mRNA和蛋白水平未受影响。我们的计算机模拟研究确定了10个TTAG(基因)在子宫内膜异位症患者的分泌中期子宫内膜中发生改变。高水平 的hTERC和其他已确定的TTAG可能是子宫内膜异位症患者在位子宫内膜端粒酶生物学既定改变的一部分,我们的数据为未来研究揭示端粒酶在子宫内膜异位症发病机制中的根本作用提供了信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/283f/7764055/f79ddc532cb6/biomedicines-08-00588-g001.jpg

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