Context: In thyroid tumors, reduced radioiodine uptake is associated with worse patient outcome concomitantly with low sodium/iodide symporter (NIS) mRNA expression. Previous studies showed that CpG-island methylation in the NIS proximal promoter does not correlate with mRNA expression.
Objectives: The aim of the study was to identify new CpG-islands within the NIS 5'region and investigate the involvement of their methylation in NIS expression.
Design: DNA was obtained from 30 pairs of thyroid samples: tumor (T) and surrounding nontumor (NT) samples. All T samples had reduced NIS mRNA expression compared to NT samples.
Main Outcome Measures: Methylation degree was quantified by bisulfite sequencing, and NIS expression by real-time PCR and Western blot. Reporter gene assays were performed to determine CpG-island functionality. Tumor cell cultures were treated with 5-Aza demethylating agent to determine NIS expression, methylation status, and (125)I uptake.
Results: We identified a new CpG-island2 with 14 CpG sites, located -2152/-1887 relative to ATG site. CpG-island2 was hypermethylated in T compared to NT samples, in both benign and malignant tumor groups. There was a significant inverse correlation between NIS mRNA expression and degree of CpG-island2 methylation in NT and T samples. This sequence increased the expression of a reporter gene; thus, it was considered a new enhancer. Cell culture treatments with 5-Aza reduced CpG-island2 methylation levels concomitantly with restoration of NIS mRNA and protein expression and (125)I uptake.
Conclusions: We identified a new distal enhancer, NIS distal enhancer, that regulates gene expression through DNA methylation. This enhancer is hypermethylated in T compared to NT samples and is associated with decreased NIS expression in tumors. This epigenetic deregulation may be an early event in tumorigenesis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1210/jc.2013-1450 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Per- and polyfluoroalkyl substances (PFAS) exposure is associated with radioiodine therapy resistance and dedifferentiation of differentiated thyroid cancer.
Environ Pollut
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:
Differentiated thyroid cancer (DTC) generally has a favorable prognosis, and radioactive iodine (RAI) therapy is typically used for metastatic DTC that continues to progress and poses life-threatening risks. However, resistance to RAI in metastatic DTC significantly impairs treatment effectiveness. This study aims to identify potential compounds that may influence RAI efficacy.
View Article and Find Full Text PDFFunctional characterization of novel compound heterozygous missense gene variants causing congenital dyshormonogenic hypothyroidism.
Front Endocrinol (Lausanne)
January 2025
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis.
Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands.
Oncolytic measles virus-induced cell killing in radio-resistant and drug-resistant nasopharyngeal carcinoma.
Malays J Pathol
December 2024
Universiti Tunku Abdul Rahman, M. Kandiah Faculty of Medicine and Health Sciences, Department of Pre-clinical Sciences, Bandar Sungai Long, 43000, Kajang, Selangor, Malaysia.
Introduction: The current first-line therapy for nasopharyngeal carcinoma (NPC) is often associated with long-term complications. Oncolytic measles virus (MV) therapy offers a promising alternative to cancer therapy. This study aims to investigate the efficacy of MV in killing NPC cells in vitro, both with or without resistance to radiation and drug therapy.
View Article and Find Full Text PDFLow Renalase Levels in Newly Diagnosed CML: Dysregulation Sensitive to Modulation by Tyrosine Kinase Inhibitors.
Pathophysiology
December 2024
Department of Pathophysiology, University of Nis, Faculty of Medicine, 18000 Nis, Serbia.
A dysregulated proinflammatory microenvironment is considered one of the reasons why current therapies of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI) do not secure disease control. Therefore, the development of BCR-ABL1-independent therapies is encouraged. Renalase (RNLS) is a multifunctional protein that exhibits both enzymatic and non-enzymatic cytokine-like properties, along with potent anti-inflammatory and anti-apoptotic effects.
View Article and Find Full Text PDFNIS-Seq enables cell-type-agnostic optical perturbation screening.
Nat Biotechnol
December 2024
Institute of Clinical Chemistry and Clinical Pharmacology, University and University Hospital Bonn, Bonn, Germany.
Optical pooled screening offers a broader-scale alternative to enrichment-based perturbation screening, using fluorescence microscopy to correlate phenotypes and perturbations across single cells. Previous methods work well in large, transcriptionally active cell lines, because they rely on cytosolic detection of endogenously expressed barcoded transcripts; however, they are limited by reliable cell segmentation, cytosol size, transcriptional activity and cell density. Nuclear In-Situ Sequencing (NIS-Seq) expands this technology by creating bright sequencing signals directly from nuclear genomic DNA to screen nucleated cells at high density and high library complexity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!