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Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer
Published on: June 9, 2023
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A TIMELESS link to dedifferentiation in thyroid cancer
Jie-Jen Lee1,2, Yi-Chiung Hsu3,4,5, Chi-Yu Kuo1,2
1Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan.
The Journal of Endocrinology
|October 8, 2025
Summary
TIMELESS gene expression increases with thyroid cancer progression. Targeting TIMELESS may enhance thyroid cancer treatments and reduce tumor growth.
Area of Science:
- Molecular Biology
- Cancer Research
- Chronobiology
Background:
- TIMELESS (a circadian clock gene) is implicated in cell cycle regulation.
- TIMELESS is upregulated in dedifferentiated thyroid cancer, but its role is unclear.
Purpose of the Study:
- To investigate TIMELESS expression and functional significance in thyroid neoplasms.
- To evaluate TIMELESS as a potential therapeutic target in thyroid cancer.
Main Methods:
- Bioinformatics analysis of The Cancer Genome Atlas (TCGA) data.
- Immunoblotting and immunohistochemistry to assess TIMELESS protein levels.
- In vitro (cell lines) and in vivo (xenograft models) functional studies.
Main Results:
- TIMELESS expression increases progressively from normal thyroid tissue to differentiated and anaplastic thyroid cancer.
- TIMELESS knockdown inhibits cancer cell proliferation, spheroid formation, and xenograft growth.
- Reduced TIMELESS levels correlate with lower recombination scores and increased sensitivity to doxorubicin.
- Knockdown upregulates NKX2-1 and SLC5A5 mRNA expression.
Conclusions:
- TIMELESS overexpression is linked to thyroid cancer dedifferentiation.
- TIMELESS represents a potential therapeutic target for combination therapies in thyroid cancer.
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