Telomere transcripts act as tumor suppressor and are associated with favorable prognosis in colorectal cancer with low proliferating cell nuclear antigen expression.

Autor: Kienzl P; 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., Deloria AJ; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria.; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria., Hunjadi M; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Hadolt JM; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Haering MF; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Bothien A; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Mejri D; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Korkut-Demirbaş M; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Sampl S; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Weber G; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Pirker C; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Laengle S; Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria., Braunschmid T; Department of Surgery, Social Medical Center South, Kaiser Franz Josef Hospital, Vienna, Austria.; Department of Surgery, Klinik Floridsdorf, Wiener Gesundheitsverbund, Vienna, Austria., Dragona E; Laboratory of Genetics Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece (BRFAA), Soranou Efesiou 4, Athens, 115 27, Greece., Marian B; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Gagos S; Laboratory of Genetics Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece (BRFAA), Soranou Efesiou 4, Athens, 115 27, Greece., Lu L; Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, USA., Henson JD; Prince of Wales Clinical School, University of NSW, UNSW, Sydney, 2052, Australia., Lau LMS; Children's Cancer Research Unit, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Westmead, 2145, Australia., Reddel RR; Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, 2145, Australia., Mikulits W; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria., Stättner S; Department of Surgery, Social Medical Center South, Kaiser Franz Josef Hospital, Vienna, Austria.; Department of General, Visceral and Vascular Surgery, Salzkammergut Klinikum, OÖG, Dr. Wilhelm Bock Strasse 1, Vöcklabruck, 4840, Austria., Holzmann K; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria. klaus.holzmann@meduniwien.ac.at.
Jazyk: angličtina
Zdroj: Cellular oncology (Dordrecht, Netherlands) [Cell Oncol (Dordr)] 2024 Sep 02. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1007/s13402-024-00986-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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