Dicer1 Depletion Leads to DNA Damage Accumulation and Cell Death in a RET/PTC3 Papillary Thyroid Cancer Mouse Model,

Maria Rojo-Pardillo1, Alice Augenlicht1, Geneviève Dom1

  • 1IRIBHM J. E. Dumont, Université Libre de Bruxelles,1070 Brussels, Belgium.

Cells
|September 26, 2025
PubMed

Insights

Dicer1 dosage is critical in thyroid cancer. Partial loss did not affect tumor growth, but complete Dicer1 loss suppressed papillary thyroid carcinoma (PTC) growth by causing DNA damage and cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA (miRNA) dysregulation is implicated in thyroid tumorigenesis.
  • Dicer1, essential for miRNA maturation, is frequently downregulated in papillary thyroid carcinoma (PTC).
  • Dicer1 acts as a context-dependent haplo-insufficient tumor suppressor, with partial loss potentially promoting and complete loss inhibiting tumor development.

Purpose of the Study:

  • To investigate the effects of partial (heterozygous) and complete (homozygous) Dicer1 loss in a RET/PTC3 transgenic mouse model of papillary thyroid carcinoma.
  • To elucidate the role of Dicer1 dosage in thyroid cancer progression and identify potential therapeutic targets.

Main Methods:

  • Genetic inactivation of one or both Dicer1 alleles in thyroid follicular cells of RET/PTC3 transgenic mice using an inducible Cre-Lox system.
  • Analysis of tumor progression, cell characteristics (vimentin expression), redox homeostasis, DNA damage, and cell death.

Main Results:

  • Heterozygous Dicer1 loss did not alter tumor progression in the RET/PTC3 model.
  • Homozygous Dicer1 loss reduced tumor growth, increased DNA damage, and induced cell death.
  • Dicer1 loss was associated with increased vimentin-positive cells and disrupted redox homeostasis.

Conclusions:

  • Dicer1 dosage plays a crucial role in thyroid cancer progression.
  • Complete Dicer1 loss can suppress tumor growth, suggesting its potential as a therapeutic target in aggressive PTC and other cancers with altered Dicer1 expression.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.0K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.3K