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Volume 47
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation

by
Adrian Albulescu
1,2,
Alina Fudulu
1,*,
Mirela Antonela Mihaila
3,
Iulia Iancu
1,
Adriana Plesa
1,
Marinela Bostan
3,
Anca Botezatu
1,
Lorelei Irina Brasoveanu
3,* and
Camelia Mia Hotnog
3
1
Molecular Virology Department, Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
2
Pharmacology Department, National Institute for Chemical Pharmaceutical Research and Development, 031299 Bucharest, Romania
3
Center of Immunology, Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
*
Authors to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2025, 47(10), 863; https://doi.org/10.3390/cimb47100863
Submission received: 10 September 2025 / Revised: 13 October 2025 / Accepted: 16 October 2025 / Published: 18 October 2025
(This article belongs to the Special Issue Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy)
Versions Notes

Abstract

Thyroid carcinomas are phenotypically heterogeneous malignancies. Advances in molecular and cellular technologies have revealed genetic, epigenetic, and nongenetic factors underlying this heterogeneity. Our study aimed to assess the impact of single and combined treatments with anticancer agents (Carboplatin, Doxorubicin, Paclitaxel, Avastin), natural compounds (Quercetin), and epigenetic modulators (suberoylanilide hydroxamic acid and 5-Azacytidine) on the expression of long noncoding RNAs, methylation regulators, and functional features in the human thyroid cancer cell line K1. Methods: Treated and untreated K1 cells were used throughout experiments to evaluate the drug-induced cytotoxicity, apoptosis, cell cycle distribution, cytokine release, gene expression, and global DNA methylation levels. Results: Some single- and combined-drug treatments modulated both cell cycle progression and apoptotic events, demonstrating anti-tumor activity of the tested compounds. Gene expression analysis showed treatment-specific regulation of target genes and lncRNAs, including both upregulation and downregulation across different drug combinations. All treatments resulted in increased global DNA methylation levels compared to the untreated controls. Several combinations significantly upregulated DNMT1 and DNMT3B, while concomitantly decreased EZH2 levels. Conclusions: These coordinated epigenetic changes highlight the therapeutic potential of combining epigenetic modulators with chemotherapeutic agents, suggesting a strategy to prevent or reverse treatment resistance and improve outcomes in thyroid cancer patients.
Keywords: lncRNAs; epigenetics; thyroid cancer; K1 human cell line; methylation; apoptosis; cell cycle; cytokine release lncRNAs; epigenetics; thyroid cancer; K1 human cell line; methylation; apoptosis; cell cycle; cytokine release

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MDPI and ACS Style

Albulescu, A.; Fudulu, A.; Mihaila, M.A.; Iancu, I.; Plesa, A.; Bostan, M.; Botezatu, A.; Brasoveanu, L.I.; Hotnog, C.M. Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation. Curr. Issues Mol. Biol. 2025, 47, 863. https://doi.org/10.3390/cimb47100863

AMA Style

Albulescu A, Fudulu A, Mihaila MA, Iancu I, Plesa A, Bostan M, Botezatu A, Brasoveanu LI, Hotnog CM. Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation. Current Issues in Molecular Biology. 2025; 47(10):863. https://doi.org/10.3390/cimb47100863

Chicago/Turabian Style

Albulescu, Adrian, Alina Fudulu, Mirela Antonela Mihaila, Iulia Iancu, Adriana Plesa, Marinela Bostan, Anca Botezatu, Lorelei Irina Brasoveanu, and Camelia Mia Hotnog. 2025. "Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation" Current Issues in Molecular Biology 47, no. 10: 863. https://doi.org/10.3390/cimb47100863

APA Style

Albulescu, A., Fudulu, A., Mihaila, M. A., Iancu, I., Plesa, A., Bostan, M., Botezatu, A., Brasoveanu, L. I., & Hotnog, C. M. (2025). Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation. Current Issues in Molecular Biology, 47(10), 863. https://doi.org/10.3390/cimb47100863

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