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

被引:14
作者
Alnafakh, Rafah [1 ,2 ]
Choi, Fiona [1 ]
Bradfield, Alice [1 ]
Adishesh, Meera [1 ,3 ]
Saretzki, Gabriele [4 ]
Hapangama, Dharani K. [1 ,3 ]
机构
[1] Univ Liverpool, Inst Life Course & Med Sci, Dept Womens & Childrens Hlth, Member Liverpool Hlth Partners, Liverpool L8 7SS, Merseyside, England
[2] Al Hilla Teaching Hosp, Dept Pathol, Babil 51001, Iraq
[3] Liverpool Womens Hosp NHS Fdn Trust, Liverpool Hlth Partners, Liverpool L8 7SS, Merseyside, England
[4] Univ Newcastle, Biosci Inst, Campus Ageing & Vital, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
关键词
hTERC; DKC1; dyskerin; telomere; telomerase; endometriosis; HUMAN-PAPILLOMAVIRUS E6; TELOMERASE ACTIVITY; ABERRANT EXPRESSION; EPITHELIAL-CELLS; RNA EXPRESSION; CANCER-CELLS; WOMEN; PATHOGENESIS; DYSKERIN; HEALTHY;
D O I
10.3390/biomedicines8120588
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (n = 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 (CDKN2A, PML, ZNHIT2, UBE3A, MCCC2, HSPC159, FGFR2, PIK3C2A, RALGAPA1, and HNRNPA2B1) 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.
引用
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页码:1 / 21
页数:21
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