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Human endometrial carcinogenesis is associated with significant reduction in long non-coding RNA, TERRA

Adishesh, Meera, Alnafakh, Rafah, Baird, Duncan, Jones, Rhiannon E., Simon, Shannon, Button, Lucy, Kamal, Areege, Kirwan, John, DeCruze, S. Bridget, Drury, Josephine, Saretzki, Gabriele and Hapangama, Dharani K. 2020. Human endometrial carcinogenesis is associated with significant reduction in long non-coding RNA, TERRA. International Journal of Molecular Sciences 21 (22) , 8686. 10.3390/ijms21228686

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Abstract

Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy (n = 23) and pathological (n = 24) human endometrium and to examine their association with cellular proliferation, TA and telomere lengths. EC samples demonstrated significantly reduced levels of TERRAs for Chromosome 16p (Ch-16p) (p < 0.002) and Chromosome 20q (Ch-20q) (p = 0.0006), when compared with the postmenopausal samples. No significant correlation was found between TERRA levels and TA but both Ch-16p and Ch-20q TERRA levels negatively correlated with the proliferative marker Ki67 (r = −0.35, p = 0.03 and r = −0.42, p = 0.01 respectively). Evaluation of single telomere length analysis (STELA) at XpYp telomeres demonstrated a significant shortening in EC samples when compared with healthy tissues (p = 0.002). We detected TERRAs in healthy human endometrium and observed altered individual TERRA-specific levels in malignant endometrium. The negative correlation of TERRAs with cellular proliferation along with their significant reduction in EC may suggest a role for TERRAs in carcinogenesis and thus future research should explore TERRAs as potential therapeutic targets in EC.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Publisher: MDPI
ISSN: 1661-6596
Date of First Compliant Deposit: 20 November 2020
Date of Acceptance: 16 November 2020
Last Modified: 07 Dec 2020 11:04
URI: http://orca.cf.ac.uk/id/eprint/136548

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