{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:10:07Z","timestamp":1790363407105,"version":"4.1.0"},"reference-count":93,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veneto Institute of Oncology, IOV-IRCCS, 5x1000 2017\u2014Cancer Genomics Research Platform","award":["GIUN_BIRD21_01"],"award-info":[{"award-number":["GIUN_BIRD21_01"]}]},{"name":"University of Padova","award":["GIUN_BIRD21_01"],"award-info":[{"award-number":["GIUN_BIRD21_01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Telomerase reverse transcriptase (TERT), the catalytic component of telomerase, may also contribute to carcinogenesis via telomere-length independent mechanisms. Our previous in vitro and in vivo studies demonstrated that short-term telomerase inhibition by BIBR1532 impairs cell proliferation without affecting telomere length. Here, we show that the impaired cell cycle progression following short-term TERT inhibition by BIBR1532 in in vitro models of B-cell lymphoproliferative disorders, i.e., Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs), and B-cell malignancies, i.e., Burkitt\u2019s lymphoma (BL) cell lines, is characterized by a significant reduction in NF-\u03baB p65 nuclear levels leading to the downregulation of its target gene MYC. MYC downregulation was associated with increased expression and nuclear localization of P21, thus promoting its cell cycle inhibitory function. Consistently, treatment with BIBR1532 in wild-type zebrafish embryos significantly decreased Myc and increased p21 expression. The combination of BIBR1532 with antineoplastic drugs (cyclophosphamide or fludarabine) significantly reduced xenografted cells\u2019 proliferation rate compared to monotherapy in the zebrafish xenograft model. Overall, these findings indicate that short-term inhibition of TERT impairs cell growth through the downregulation of MYC via NF-\u03baB signalling and supports the use of TERT inhibitors in combination with antineoplastic drugs as an efficient anticancer strategy.<\/jats:p>","DOI":"10.3390\/cancers15102673","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T01:57:51Z","timestamp":1683683871000},"page":"2673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach"],"prefix":"10.3390","volume":"15","author":[{"given":"Aamir","family":"Amin","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-3820","authenticated-orcid":false,"given":"Marzia","family":"Morello","sequence":"additional","affiliation":[{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV\u2014IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Raffaella","family":"Petrara","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4243-4363","authenticated-orcid":false,"given":"Beatrice","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV\u2014IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0803-8236","authenticated-orcid":false,"given":"Francesco","family":"Argenton","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-7509","authenticated-orcid":false,"given":"Anita","family":"De Rossi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, 35128 Padova, Italy"},{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV\u2014IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-1478","authenticated-orcid":false,"given":"Silvia","family":"Giunco","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, 35128 Padova, Italy"},{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV\u2014IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41580-020-0234-z","article-title":"Regulation of human telomerase in homeostasis and disease","volume":"21","author":"Roake","year":"2020","journal-title":"Nat. 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