Philip Kienzl, Abigail J Deloria, Monika Hunjadi, Juliane M Hadolt, Max-Felix Haering, Angrit Bothien, Doris Mejri, Medina Korkut-Demirbaş, Sandra Sampl, Gerhard Weber, Christine Pirker, Severin Laengle, Tamara Braunschmid, Eleni Dragona, Brigitte Marian, Sarantis Gagos, Lingeng Lu, Jeremy D Henson, Loretta M S Lau, Roger R Reddel, Wolfgang Mikulits, Stefan Stättner, Klaus Holzmann
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引用次数: 0
摘要
含端粒重复序列的RNA(TERRA)和端粒酶RNA成分(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标志来促进端粒平衡。此外,端粒酶逆转录酶(TERT)和TERRA的非规范功能似乎参与了上皮-间充质转化(EMT),而EMT对癌症进展非常重要。然而,TERRA与患者预后之间的关系尚未完全定性。在这项小规模研究中,研究人员评估了68名结直肠癌(CRC)患者的端粒生物学、增殖和EMT基因转录物与疾病预后之间的相关性。增殖细胞核抗原(PCNA)和上皮剪接调节蛋白 1 和 2(ESRP1 和 ESRP2)与 TERRA 呈正相关,而 TA 与 TERRA 呈反相关。与之前的研究结果一致,本研究发现,与邻近的非肿瘤组织相比,CRC 肿瘤组织中 TERT 和 TERC 的表达水平较高,TA 和 TL 的表达水平也有所增加。相比之下,肿瘤组织中 TERRA 的表达水平较低。与反向模式的患者相比,TERRA表达量高而PCNA水平低的患者总体生存率较高。此外,TERRA 还能抑制重症联合免疫缺陷病(SCID)小鼠的 CRC 肿瘤生长。总之,我们的研究扩展了以前发表的有关 TERRA 的研究,表明它在端粒酶阳性的 CRC 中具有潜在的治疗作用。
Telomere transcripts act as tumor suppressor and are associated with favorable prognosis in colorectal cancer with low proliferating cell nuclear antigen expression.
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.
期刊介绍:
The Official Journal of the International Society for Cellular Oncology
Focuses on translational research
Addresses the conversion of cell biology to clinical applications
Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions.
A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients.
In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.