A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Dicer1 Depletion Leads to DNA Damage Accumulation and Cell Death in a RET/PTC3 Papillary Thyroid Cancer Mouse Model, Thereby Inhibiting Tumor Progression
Tekijät: Rojo-Pardillo, Maria; Augenlicht, Alice; Dom, Geneviève; Kero, Jukka; Robaye, Bernard; Maenhaut, Carine
Kustantaja: MDPI AG
Julkaisuvuosi: 2025
Lehti:: Cells
Tietokannassa oleva lehden nimi: CELLS
Artikkelin numero: 1465
Vuosikerta: 14
Numero: 18
ISSN: 2073-4409
eISSN: 2073-4409
DOI: https://doi.org/10.3390/cells14181465
Verkko-osoite: https://doi.org/10.3390/cells14181465
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/504540090
Beyond well-known genetic drivers, microRNA dysregulation has emerged as a key contributor to thyroid tumorigenesis. Central to this process is Dicer1, a ribonuclease essential for microRNA maturation, whose expression is often reduced in papillary thyroid carcinoma (PTC). Evidence from previous studies suggest Dicer1 functions as a context-dependent haplo-insufficient tumor suppressor gene: partial loss may promote tumor development, whereas complete loss may disrupt essential cellular functions, causing cell death and tumor suppression. However, the effects of partial or complete Dicer1 loss in thyroid cancer remain unclear. To explore this, we genetically inactivated one (heterozygous) or both (homozygous) Dicer1 alleles specifically in thyroid follicular cells of a RET/PTC3 transgenic mouse model using an inducible Cre-Lox system. Our findings deepen the current understanding of the RET/PTC3-driven PTC model by revealing an increased number of vimentin-positive cells and disruption in redox homeostasis. Additionally, whereas heterozygous Dicer1 loss did not alter tumor progression in RET/PTC3 mice, total loss reduced tumor growth and led to accumulated DNA damage and cell death. These findings highlight the crucial role of Dicer1 dosage in thyroid cancer progression and underscore its potential as a therapeutic target for aggressive PTC and other malignancies characterized by aberrant Dicer1 expression.
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This research was funded by the Fund for Scientific Research—Research credit (CDR J.0123.23 and CDR J.0150.25), Jaumotte-Demoulin Foundation (Université libre de Bruxelles), Fund for Scientific Research—FRIA grant (FC36079), King Baudouin Foundation (Fund Doctor J.P. Naets, grants 2023-J1813300-233020 and 2025-J1813300-0025101), Rose et Jean Hoguet Foundation, David et Alice Van Buuren Foundation and Héger-Masson Foundation. Author J.K. was supported by the Sigrid Jusélius Foundation (grant no. 115-1956-26) and the Novo Nordisk Foundation (grant
no. 0078329).
