2. Academic Validation
  3. Overexpression of NR1D1 Portends Disease Recurrence in Thyroid Cancer

Overexpression of NR1D1 Portends Disease Recurrence in Thyroid Cancer

  • J Clin Endocrinol Metab. 2025 Mar 17;110(4):991-1002. doi: 10.1210/clinem/dgae687.
Yi-Chiung Hsu 1 2,  Chi-Yu Kuo 3 4,  Ming-Nan Chien 4 5,  Jie-Yang Jhuang 4 6,  Shih-Yuan Huang 7,  Shao-Chiang Chang 7,  Shih-Ping Cheng 3 4 7 8 9
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320317, Taiwan.
  • 2 Center for Astronautical Physics and Engineering, National Central University, Taoyuan 320317, Taiwan.
  • 3 Department of Surgery, MacKay Memorial Hospital, Taipei 104217, Taiwan.
  • 4 Department of Medicine, School of Medicine, MacKay Medical College, New Taipei City 252005, Taiwan.
  • 5 Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104217, Taiwan.
  • 6 Department of Pathology, MacKay Memorial Hospital, Taipei 104217, Taiwan.
  • 7 Department of Medical Research, MacKay Memorial Hospital, Taipei 104217, Taiwan.
  • 8 Institute of Biomedical Sciences, MacKay Medical College, New Taipei City 252005, Taiwan.
  • 9 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan.
PMID: 39359072 DOI: 10.1210/clinem/dgae687
Abstract

Context: Dysregulation of circadian rhythms has been linked to Cancer susceptibility. Thyroid Cancer cells demonstrate altered circadian oscillations in endogenous clock transcripts.

Objective: Our previous research identified NR1D1, a component of the circadian clock, as one of the recurrence-associated genes in papillary thyroid Cancer. The objective of this study was to investigate the expression pattern of NR1D1 in thyroid Cancer and explore its prognostic and translational implications.

Methods: We assessed NR1D1 expression using immunohistochemical analysis and examined its correlation with clinicopathological parameters. In vitro and in vivo experiments were performed to elucidate the oncogenic roles of NR1D1 and potential mechanisms.

Results: Nuclear NR1D1 expression was present in thyroid follicular epithelial-derived cancers, whereas normal thyroid tissue and benign nodular goiter showed no detectable NR1D1 immunoreactivity. Patients with high expression of NR1D1 had more advanced disease stages, extrathyroidal extension, lymphovascular invasion, and shorter recurrence-free survival compared to those with low levels of NR1D1. Through gain- and loss-of-function studies, we demonstrated that NR1D1 modulation affected the growth of organoids, resistance to anoikis, and the invasive and migratory capacity of thyroid Cancer cells. The invasion-promoting effect of NR1D1 was regulated by the β-catenin/ZEB1 axis. Moreover, the overexpression of NR1D1 accelerated xenograft growth and lung metastasis in vivo.

Conclusion: NR1D1 is overexpressed in malignant thyroid tumors and has prognostic significance. Our findings suggest therapeutic potential in targeting NR1D1 for thyroid Cancer.

Keywords

NR1D1; cell adhesion; recurrence; thyroid cancer; β-catenin.

Figures
Products