Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan)-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City 14080, Mexico.
Wellcome Centre for Cell Biology, Institute of Cell Biology (ICB), University of Edinburgh, Edinburgh EH9 3BF, UK.
Int J Mol Sci. 2022 Mar 18;23(6):3271. doi: 10.3390/ijms23063271.
The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.
长非编码 RNA（lncRNA）端粒重复 RNA（TERRA）与端粒稳态、端粒酶募集和染色体修复过程有关；然而，在致癌过程中尚未研究这种关联的影响。确定 TERRA 表达的变化是细胞转化的原因还是结果是一项复杂的任务，因为研究通常使用癌细胞或肿瘤样本进行。为了确定这种长非编码 RNA 在细胞衰老和染色体修复中的作用，我们在建立未转化髓样细胞克隆的过程中评估了端粒的完整性和 TERRA 的表达。我们发现，TERRA 的表达减少会扰乱某些基因座的端粒稳态，但只有当亚端粒双价染色质域的甲基化受到损害时，lncRNA 的表达才会受到影响。我们得出结论，TERRA 稳态的破坏是细胞转化的结果，其表达谱的变化可导致端粒和基因组不稳定。
