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Methylation levels of sodium-iodide symporter (NIS) promoter in benign and malignant thyroid tumors with reduced NIS expression. 2013

A L Galrão, and A K Sodré, and R Y Camargo, and C U Friguglietti, and M A Kulcsar, and E U Lima, and G Medeiros-Neto, and I G S Rubio
Thyroid Unit, Cellular and Molecular Endocrine Laboratory, LIM-25, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.

DNA methylation regulates gene expression. Aberrant methylation plays an important role in human tumorigenesis. We have previously detected reduced NIS mRNA expression in thyroid tumors as compared to non-tumor tissues. Thus, in this study we investigated whether the methylation of the CpG-island located in the NIS gene promoter was associated with reduced mRNA expression in thyroid tumors. Methylation levels of 30 pairs of samples from 10 benign and 20 malignant thyroid tumors (T) along with matched non-tumor (NT) areas were determined by semiquantitative methylation specific-PCR. NIS methylation was detected in all samples. Methylation levels and frequencies did not differ between the groups and were not associated with BRAF mutational status. Highest methylation levels and frequencies were detected in the 5' region of the CpG-island decreasing toward the 3' end. Intraindividual analysis (T versus NT) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression. No quantitative correlation was detected between methylation levels and mRNA expression in any the groups. The results of this study showed that methylation of NIS promoter is a very frequent event in both benign and malignant tumors as well as in their surrounding tissues, and characterized a non-homogeneous methylation pattern along the CpG island. Therefore, further investigations involving other sites that may be implicated in methylation regulation of NIS expression are warranted.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013961 Thyroid Gland A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively. Thyroid,Gland, Thyroid,Glands, Thyroid,Thyroid Glands,Thyroids
D013964 Thyroid Neoplasms Tumors or cancer of the THYROID GLAND. Cancer of Thyroid,Thyroid Cancer,Cancer of the Thyroid,Neoplasms, Thyroid,Thyroid Adenoma,Thyroid Carcinoma,Adenoma, Thyroid,Adenomas, Thyroid,Cancer, Thyroid,Cancers, Thyroid,Carcinoma, Thyroid,Carcinomas, Thyroid,Neoplasm, Thyroid,Thyroid Adenomas,Thyroid Cancers,Thyroid Carcinomas,Thyroid Neoplasm

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