Prognostic significance of sodium iodide symporter and deiodinase enzymes mRNA expression in gastric cancer

Abstract Context: Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS. Objectives and Methods: The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by 125I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone. Results: Iodide inhibited NIS mRNA and membrane protein expression as well as 125I uptake, which were paralleled by decreased βhCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol. Conclusions: We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression.

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Decreased Expression of Thyroglobulin and Sodium Iodide Symporter Genes in Hashimoto’s Thyroiditis

International Journal of Endocrinology ◽

10.1155/2014/690704 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Anna Popławska-Kita ◽

Beata Telejko ◽

Katarzyna Siewko ◽

Maria Kościuszko-Zdrodowska ◽

Natalia Wawrusewicz-Kurylonek ◽

...

Keyword(s):

Mrna Expression ◽

Hashimoto’S Thyroiditis ◽

Sodium Iodide ◽

Interleukin 1 ◽

Thyroid Volume ◽

Needle Aspiration ◽

Hashimoto's Thyroiditis ◽

Sodium Iodide Symporter ◽

Thyroid Cells ◽

Iodide Transport

Aim. The aim of the study was to compare the expression of sodium iodide symporter (NIS), thyroglobulin (Tg), tumor necrosis factor-α(TNFα), and interleukin-1βgenes in patients with Hashimoto’s thyroiditis (HT) and healthy individuals.Subjects and Methods.Thyroid cells were obtained from 39 patients with HT and 15 controls by an ultrasound guided fine needle aspiration biopsy.Results. The patients with HT had lower Tg and NIS mRNA (P=0.002andP=0.001, resp.), as well as higher TNFαmRNA expression (P=0.049) than the controls. In the HT group Tg mRNA expression correlated positively with NIS mRNA expression (R=0.739,P=0.0001) and thyroid volume (R=0.465,P=0.0005), as well as negatively with TNFαmRNA expression (R=-0.490,P=0.001) and anti-peroxidase antibodies (TPOAb) level (R=-0.482,P=0.0002), whereas NIS mRNA expression correlated positively with thyroid volume (R=0.319,P=0.02), as well as negatively with TNFαmRNA expression (R=-0.529,P=0.0006) and TPOAb level (R=-0.422,P=0.001).Conclusions.Our results suggest that decreased Tg and NIS expression in thyroid cells may result in reduced active iodide transport and reduced thyroid volume in patients with HT.

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Sodium/iodide symporter mRNA expression in cold thyroid nodules

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2001-11013 ◽

2001 ◽

Vol 109 (01) ◽

pp. 45-46 ◽

Cited By ~ 2

Author(s):

R. Paschke ◽

S. Neumann

Keyword(s):

Mrna Expression ◽

Sodium Iodide ◽

Thyroid Nodules ◽

Sodium Iodide Symporter ◽

Cold Thyroid Nodules

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Prognostic values of E2F mRNA expression in human gastric cancer

Bioscience Reports ◽

10.1042/bsr20181264 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 12

Author(s):

Theasha Manicum ◽

Fubiao Ni ◽

Yiming Ye ◽

Xuhui Fan ◽

Bi-Cheng Chen

Keyword(s):

Gastric Cancer ◽

Transcription Factors ◽

Mrna Expression ◽

Prognostic Significance ◽

Family Members ◽

Incidence Rates ◽

Human Gastric Cancer ◽

Kaplan Meier ◽

E2f Transcription Factors ◽

Transcription Activators

Gastric cancer (GC) is the second most frequent cause of cancer-related mortality in the world, with Eastern Asia having the highest incidence rates. E2F is a family of transcription factor proteins that has a variety of functions, which include control of cell cycle, cell differentiation, DNA damage response and cell death. E2F transcription factors are divided into two subfamilies: transcription activators (E2F transcription factors 1 (E2F1), 2 (E2F2) and 3a (E2F3a)) and repressors (E2F3b, E2F transcription factors 4 (E2F4), 5 (E2F5), 6 (E2F6), 7 (E2F7) and 8 (E2F8)). Studies have demonstrated that E2F had prognostic significance in a number of cancers. However, the entirety of the prognostic roles of E2F mRNA expression in GC has not yet been apparently determined. In the present study, the prognostic value of individual family members of E2F mRNA expression for overall survival (OS) was evaluated by using online Kaplan–Meier Plotter (KM Plotter) database. Our result demonstrated that high expressions of three family members of E2F (E2F1, E2F3, E2F4) mRNA were significantly associated with unfavourable OS in all GC patients. However, increased expressions of E2F2, E2F5, E2F6 and E2F7 were significantly associated with favourable OS, especially for higher clinical stages in GC patients. These results provided a better insight into the prognostic functions of E2F mRNA genes in GC. Although the results should be further verified in clinical trials, our findings may be a favourable prognostic predictor for the development of newer therapeutic drugs in the treatment of GC.

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Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

AJP Cell Physiology ◽

10.1152/ajpcell.00224.2009 ◽

2010 ◽

Vol 298 (4) ◽

pp. C893-C899 ◽

Cited By ~ 29

Author(s):

Caroline Serrano-Nascimento ◽

Jamile Calil-Silveira ◽

Maria Tereza Nunes

Keyword(s):

Mrna Expression ◽

Posttranscriptional Regulation ◽

Sodium Iodide ◽

Tail Length ◽

Northern Blotting ◽

Mrna Abundance ◽

Translation Efficiency ◽

Sodium Iodide Symporter ◽

Hormone Synthesis ◽

Rat Thyroid

Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-β increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of Wolff-Chaikoff effect. We investigated whether acute iodide administration could trigger events that precede those changes, such as reduction of sodium-iodide symporter (NIS) mRNA abundance and adenylation, and if perchlorate treatment could counteract them. Rats subjected or not to methylmercaptoimidazole treatment (0.03%) received NaI (2,000 μg/0.5 ml saline) or saline intraperitoneally and were killed 30 min up to 24 h later. Another set of animals was treated with iodide and perchlorate, in equimolar doses. NIS mRNA content was evaluated by Northern blotting and real-time PCR, and NIS mRNA poly(A) tail length by rapid amplification of cDNA ends–poly(A) test (RACE-PAT). We observed that NIS mRNA abundance and poly(A) tail length were significantly reduced in all periods of iodide treatment. Perchlorate reversed these effects, indicating that iodide was the agent that triggered the modifications observed. Since the poly(A) tail length of mRNAs is directly associated with their stability and translation efficiency, we can assume that the rapid decay of NIS mRNA abundance observed was due to a reduction of its stability, a condition in which its translation could be impaired. Our data show for the first time that iodide regulates NIS mRNA expression at posttranscriptional level, providing a new mechanism by which iodide exerts its autoregulatory effect on thyroid.

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Prognostic values of inhibitory κB kinases mRNA expression in human gastric cancer

Bioscience Reports ◽

10.1042/bsr20180617 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 3

Author(s):

David Timothy Gayed ◽

Jayant Wodeyar ◽

Zi-Xiang Wang ◽

Xiang Wei ◽

Yi-Yi Yao ◽

...

Keyword(s):

Gastric Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Prognostic Significance ◽

Stage Iv ◽

Nuclear Factor Κb ◽

Therapeutic Interventions ◽

Human Gastric Cancer ◽

Stage Iv Gastric Cancer ◽

Diffuse Type Gastric Cancer

AbstractBackground: Inhibitory κB kinases (IKKs) play a key role in modulating proinflammatory and growth stimulating signals through their regulation of the nuclear factor κB (NF-κB) cascade. Therefore, the level of expression of IKKs represents a viable prognostic predictor with regard to various pathological processes. The prognostic value of IKKs expression in gastric cancer remains unclear. Methods: We used the ‘Kaplan–Meier plotter’ (KM plotter) online database, to explore the predictive prognostic value of individual IKKs members’ mRNA expression to overall survival (OS) in different clinical data including pathological staging, histology, and therapies employed. Results: Our results revealed that a higher mRNA expression of inhibitor of NF-κB kinase subunit α (IKKα) was correlated to better OS, whereas higher mRNA expression of IKKβ, inhibitor of NF-κB kinase subunit γ (IKKγ), inhibitor of NF-κB kinase subunit ε (IKKε), and suppressor of IKKε (SIKE) were generally correlated to unfavorable OS in gastric cancer. Increased mRNA expression of IKKε also showed better outcomes in stage IV gastric cancer. Further a correlation between elevated levels of mRNA expression of both IKKε and SIKE was found to have favorable OS in diffuse type gastric cancer. It was also revealed that high expression of SIKE had favorable OS when treated with other adjuvant therapies, while worse OS when treated only with 5FU therapy. Conclusion: Our results suggest that mRNA expression of individual IKKs and SIKE are associated with unique prognostic significance and may act as valuable prognostic biomarkers and potential targets for future therapeutic interventions in gastric cancer.

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