Kienzl Philip, Deloria Abigail J, Hunjadi Monika, Hadolt Juliane M, Haering Max-Felix, Bothien Angrit, Mejri Doris, Korkut-Demirbaş Medina, Sampl Sandra, Weber Gerhard, Pirker Christine, Laengle Severin, Braunschmid Tamara, Dragona Eleni, Marian Brigitte, Gagos Sarantis, Lu Lingeng, Henson Jeremy D, Lau Loretta M S, Reddel Roger R, Mikulits Wolfgang, Stättner Stefan, Holzmann Klaus
Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria.
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Cell Oncol (Dordr). 2025 Feb;48(1):239-247. doi: 10.1007/s13402-024-00986-y. Epub 2024 Sep 2.
Telomeric repeat-containing RNAs (TERRA) and telomerase RNA component (TERC) regulate telomerase activity (TA) and thereby contribute to telomere homeostasis by influencing telomere length (TL) and the cell immortality hallmark of cancer cells. Additionally, the non-canonical functions of telomerase reverse transcriptase (TERT) and TERRA appear to be involved in the epithelial-mesenchymal transition (EMT), which is important for cancer progression. However, the relationship between TERRA and patient prognosis has not been fully characterized. In this small-scale study, 68 patients with colorectal cancer (CRC) were evaluated for correlations between telomere biology, proliferation, and EMT gene transcripts and disease outcome. The proliferating cell nuclear antigen (PCNA) and the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) showed a positive correlation with TERRA, while TA and TERRA exhibited an inverse correlation. Consistent with previous findings, the present study revealed higher expression levels of TERT and TERC, and increased TA and TL in CRC tumor tissue compared to adjacent non-tumor tissue. In contrast, lower expression levels of TERRA were observed in tumor tissue. Patients with high TERRA expression and low PCNA levels exhibited favorable overall survival rates compared to individuals with the inverse pattern. Furthermore, TERRA suppressed CRC tumor growth in severe combined immunodeficiency disease (SCID) mice. In conclusion, our study extends previously published research on TERRA suggesting its potential therapeutic role in telomerase-positive CRC.
端粒重复序列RNA（TERRA）和端粒酶RNA组分（TERC）调节端粒酶活性（TA），从而通过影响端粒长度（TL）和癌细胞的细胞永生化特征来维持端粒稳态。此外，端粒酶逆转录酶（TERT）和TERRA的非经典功能似乎参与了上皮-间质转化（EMT），这对癌症进展很重要。然而，TERRA与患者预后之间的关系尚未完全明确。在这项小规模研究中，对68例结直肠癌（CRC）患者评估了端粒生物学、增殖和EMT基因转录本与疾病结局之间的相关性。增殖细胞核抗原（PCNA）以及上皮剪接调节蛋白1和2（ESRP1和ESRP2）与TERRA呈正相关，而TA与TERRA呈负相关。与先前的研究结果一致，本研究显示与相邻非肿瘤组织相比，CRC肿瘤组织中TERT和TERC的表达水平更高，TA和TL增加。相反，在肿瘤组织中观察到TERRA的表达水平较低。与具有相反模式的个体相比，TERRA高表达且PCNA水平低的患者总体生存率良好。此外，TERRA在严重联合免疫缺陷病（SCID）小鼠中抑制CRC肿瘤生长。总之，我们的研究扩展了先前发表的关于TERRA的研究，表明其在端粒酶阳性CRC中的潜在治疗作用。
