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https://hdl.handle.net/10316/114186
Title: | MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer | Authors: | Dinami, Roberto Pompili, Luca Petti, Eleonora Porru, Manuela D'Angelo, Carmen Di Vito, Serena Rizzo, Angela Campani, Virginia De Rosa, Giuseppe Bruna, Alejandra Serra, Violeta Mano, Miguel Giacca, Mauro Leonetti, Carlo Ciliberto, Gennaro Tarsounas, Madalena Stoppacciaro, Antonella Schoeftner, Stefan Biroccio, Annamaria |
Keywords: | miR-182-3p; target therapy; telomeres; TRF2; triple-negative breast cancer | Issue Date: | 11-Jan-2023 | Publisher: | Springer Nature | Project: | Italian Association for Cancer Research (AIRC # 21579) and Ministry of Health (CO-2019- 12369662) Ministry of Health Ricerca Corrente 2022 and intramural grant-in-aid AIRC fellowships |
Serial title, monograph or event: | EMBO Molecular Medicine | Volume: | 15 | Issue: | 1 | Abstract: | The telomeric repeat-binding factor 2 (TRF2) is a telomere-capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti-cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA-based approach to reduce TRF2 expression. By performing a high-throughput luciferase screening of 54 candidate miRNAs, we identified miR-182-3p as a specific and efficient post-transcriptional regulator of TRF2. Ectopic expression of miR-182-3p drastically reduced TRF2 protein levels in a panel of telomerase- or alternative lengthening of telomeres (ALT)-positive cancer cell lines. Moreover, miR-182-3p induced DNA damage at telomeric and pericentromeric sites, eventually leading to strong apoptosis activation. We also observed that treatment with lipid nanoparticles (LNPs) containing miR-182-3p impaired tumor growth in triple-negative breast cancer (TNBC) models, including patient-derived tumor xenografts (PDTXs), without affecting mouse survival or tissue function. Finally, LNPs-miR-182-3p were able to cross the blood-brain barrier and reduce intracranial tumors representing a possible therapeutic option for metastatic brain lesions. | URI: | https://hdl.handle.net/10316/114186 | ISSN: | 1757-4676 1757-4684 |
DOI: | 10.15252/emmm.202216033 | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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