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

Lookup NU author(s): Dr Gabriele Saretzki

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat 19 containing RNA) that participate in a variety of cellular regulatory functions. High telomerase 20 activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of 21 three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p, and 20q in healthy (n=23) 22 and pathological (n=24) human endometrium and to examine their association with cellular 23 proliferation, TA and telomere lengths. EC samples demonstrated significantly reduced levels of 24 TERRAs for Chromosome 16p (Ch-16p) (P<0.002) and Chromosome 20q (Ch-20q) (P= 0.0006), when 25 compared with the postmenopausal samples. No significant correlation was found between TERRA 26 levels and TA but both Ch-16p and Ch-20q TERRA levels negatively correlated with the proliferative 27 marker Ki67 (r=-0.35, P=0.03 and r=-0.42, P=0.01 respectively). Evaluation of single telomere length 28 analysis (STELA) at XpYp telomeres demonstrated a significant shortening in EC samples when 29 compared with healthy tissues (P=0.002). We detected TERRAs in healthy human endometrium and 30 observed altered individual TERRA-specific levels in malignant endometrium. The negative 31 correlation of TERRAs with cellular proliferation along with their significant reduction in EC may 32 suggest a role for TERRAs in carcinogenesis and thus future research should explore TERRAs as 33 potential therapeutic targets in EC.


Publication metadata

Author(s): Adishesh M, Alnafakh R, Baird DM, Jones RE, Simon S, Button L, Kamal A, Kirwan J, DeCruze SB, Drury J, Saretzki G, Hapangama D

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2020

Volume: 21

Issue: 22

Online publication date: 18/11/2020

Acceptance date: 16/11/2020

Date deposited: 17/11/2020

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: MDPI

URL: https://doi.org/10.3390/ijms21228686

DOI: 10.3390/ijms21228686

Notes: I am the senior and only author from Newcastle University and was instrumentally involved in analysing telomerase activity. I have a longlasting, successful collaboration with Liverpool University and Women's Hospital


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