Human Endometrial Carcinogenesis Is Associated with Significant Reduction in Long Non-Coding RNA, TERRA



Adishesh, Meera ORCID: 0000-0002-0928-8309, Alnafakh, Rafah, Baird, Duncan M, Jones, Rhiannon E, Simon, Shannon, Button, Lucy, Kamal, Areege M, Kirwan, John, DeCruze, S Bridget, Drury, Josephine ORCID: 0000-0002-2275-6664
et al (show 2 more authors) (2020) Human Endometrial Carcinogenesis Is Associated with Significant Reduction in Long Non-Coding RNA, TERRA. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (22). E8686-.

[thumbnail of ijms-945745-IJMS layout R1.docx] Text
ijms-945745-IJMS layout R1.docx - Author Accepted Manuscript

Download (3MB)

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 (<i>n</i> = 23) and pathological (<i>n</i> = 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) (<i>p</i> < 0.002) and Chromosome 20q (Ch-20q) (<i>p</i> = 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, <i>p</i> = 0.03 and r = -0.42, <i>p</i> = 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 (<i>p</i> = 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
Uncontrolled Keywords: TERRA, long non-coding RNA, telomerase, endometrium, telomeres, telomere length, endometrial cancer
Depositing User: Symplectic Admin
Date Deposited: 02 Dec 2020 09:23
Last Modified: 02 Feb 2024 10:14
DOI: 10.3390/ijms21228686
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3108865