{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe sodium/iodide symporter (SLC5A5), also known as NIS, is an intrinsic plasma‐membrane glycoprotein whose principal physiological function is the active uptake of iodide into thyroid follicular cells—a process essential for thyroid hormone biosynthesis. This iodide transport is achieved by a sodium‐dependent co‐transport mechanism driven by the electrochemical gradient generated by the Na⁺/K⁺‐ATPase. In addition to its central role in thyroid physiology, NIS is expressed in extrathyroidal tissues such as the salivary gland, gastric mucosa, and lactating mammary gland, where it contributes to iodide accumulation and is exploited for both diagnostic imaging and targeted radioiodine therapies in benign and malignant conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNumerous studies have elucidated the regulation of NIS expression and function. Hormonal regulators such as TSH can stimulate NIS gene transcription and enhance trafficking to the plasma membrane, while agents including retinoic acid and histone deacetylase inhibitors serve to “redifferentiate” thyroid tumors by modulating NIS expression. In thyroid and breast cancers, however, aberrant expression, intracellular mislocalization, defective glycosylation, and epigenetic modifications (for example, CpG island promoter hypermethylation) are frequently observed, correlating with reduced iodide uptake and diminished effectiveness of radioiodine treatment. In addition, microRNAs (e.g. miR-146b) and oncogenic signaling pathways (including those driven by BRAFV600E) have been implicated in the repression of NIS, suggesting that both transcriptional and posttranscriptional mechanisms influence its activity in cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "23"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its endogenous role in iodide metabolism, SLC5A5 has attracted considerable attention as a vehicle for therapeutic gene transfer and targeted radiotherapy—not only in differentiated thyroid cancer but also in extrathyroidal malignancies such as breast and hepatocellular carcinomas. Advances in our understanding of NIS’s structure–function relationships have revealed critical aspects of its plasma membrane targeting and intracellular trafficking, with regulatory partners including ARF4, VCP, and PBF influencing its cellular distribution and activity. Moreover, clinical strategies that aim to restore or enhance NIS expression through epigenetic modulation, manipulation of microRNA networks, or gene therapy approaches hold promise for overcoming radioiodine resistance in dedifferentiated tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Irene L Wapnir, Matt van de Rijn, Kent Nowels, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2002-021544"}], "href": "https://doi.org/10.1210/jc.2002-021544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12679487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12679487"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "T Kogai, K Taki, G A Brent "}, {"type": "b", "children": [{"type": "t", "text": "Enhancement of sodium/iodide symporter expression in thyroid and breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/erc.1.01143"}], "href": "https://doi.org/10.1677/erc.1.01143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16954431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16954431"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Garcilaso Riesco-Eizaguirre, Pilar Santisteban "}, {"type": "b", "children": [{"type": "t", "text": "A perspective view of sodium iodide symporter research and its clinical implications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Endocrinol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/eje.1.02257"}], "href": "https://doi.org/10.1530/eje.1.02257"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16990649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16990649"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Aigerim Bizhanova, Peter Kopp "}, {"type": "b", "children": [{"type": "t", "text": "Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2008-1437"}], "href": "https://doi.org/10.1210/en.2008-1437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19196800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19196800"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Cristina Romei, Raffaele Ciampi, Pinuccia Faviana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/ERC-07-0130"}], "href": "https://doi.org/10.1677/ERC-07-0130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18509003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18509003"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Eusebio Chiefari, Antonio Brunetti, Franco Arturi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-2-35"}], "href": "https://doi.org/10.1186/1471-2407-2-35"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12475396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12475396"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Caterina Mian, Susi Barollo, Gianmaria Pennelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2007.03008.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2007.03008.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17854396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17854396"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Katsumi Taki, Takahiko Kogai, Yoko Kanamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A thyroid-specific far-upstream enhancer in the human sodium/iodide symporter gene requires Pax-8 binding and cyclic adenosine 3',5'-monophosphate response element-like sequence binding proteins for full activity and is differentially regulated in normal and thyroid cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2002-0109"}], "href": "https://doi.org/10.1210/me.2002-0109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12351692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12351692"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Garcilaso Riesco-Eizaguirre, León Wert-Lamas, Javier Perales-Patón, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-14-3547"}], "href": "https://doi.org/10.1158/0008-5472.CAN-14-3547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26282166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26282166"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Vicki E Smith, Martin L Read, Andrew S Turnell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.045427"}], "href": "https://doi.org/10.1242/jcs.045427"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19706688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19706688"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kerstin Knoop, Marie Kolokythas, Kathrin Klutz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Image-guided, tumor stroma-targeted 131I therapy of hepatocellular cancer after systemic mesenchymal stem cell-mediated NIS gene delivery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mt.2011.93"}], "href": "https://doi.org/10.1038/mt.2011.93"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21587211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21587211"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Cinzia Puppin, Federica D'Aurizio, Angela V D'Elia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of histone acetylation on sodium iodide symporter promoter and expression of thyroid-specific transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2005-0128"}], "href": "https://doi.org/10.1210/en.2005-0128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15919754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15919754"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Krista M D La Perle, Dong Chul Kim, Nathan C Hall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of sodium/iodide symporter expression in the salivary gland."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thyroid (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/thy.2012.0571"}], "href": "https://doi.org/10.1089/thy.2012.0571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23441638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23441638"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Elisabeth Darrouzet, Sabine Lindenthal, Didier Marcellin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The sodium/iodide symporter: state of the art of its molecular characterization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamem.2013.08.013"}], "href": "https://doi.org/10.1016/j.bbamem.2013.08.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23988430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23988430"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jason A Smith, Chun-Yang Fan, Chunlai Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation status of genes in papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Otolaryngol Head Neck Surg (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archotol.133.10.1006"}], "href": "https://doi.org/10.1001/archotol.133.10.1006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17938324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17938324"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Hua V Lin, Alexander M Efanov, Xiankang Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0157298"}], "href": "https://doi.org/10.1371/journal.pone.0157298"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27322810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27322810"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sushmita Chatterjee, Renu Malhotra, Frency Varghese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative immunohistochemical analysis reveals association between sodium iodide symporter and estrogen receptor expression in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0054055"}], "href": "https://doi.org/10.1371/journal.pone.0054055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23342072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23342072"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Christine Spitzweg, John C Morris "}, {"type": "b", "children": [{"type": "t", "text": "Genetics and phenomics of hypothyroidism and goiter due to NIS mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2010.02.007"}], "href": "https://doi.org/10.1016/j.mce.2010.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20153805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20153805"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ute Süsens, Irm Hermans-Borgmeyer, Jens Urny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterisation and differential expression of two very closely related G-protein-coupled receptors, GPR139 and GPR142, in mouse tissue and during mouse development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropharmacology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuropharm.2005.11.003"}], "href": "https://doi.org/10.1016/j.neuropharm.2005.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16378626"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16378626"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Séverine Trouttet-Masson, Samia Selmi-Ruby, Françoise Bernier-Valentin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for transcriptional and posttranscriptional alterations of the sodium/iodide symporter expression in hypofunctioning benign and malignant thyroid tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)63272-5"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "63272-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15215159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15215159"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Antonio De la Vieja, Christopher S Ginter, Nancy Carrasco "}, {"type": "b", "children": [{"type": "t", "text": "Molecular analysis of a congenital iodide transport defect: G543E impairs maturation and trafficking of the Na+/I- symporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2005-0162"}], "href": "https://doi.org/10.1210/me.2005-0162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15976004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15976004"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "N Caraccio, R Giannini, S Cuccato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type I interferons modulate the expression of thyroid peroxidase, sodium/iodide symporter, and thyroglobulin genes in primary human thyrocyte cultures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2004-1173"}], "href": "https://doi.org/10.1210/jc.2004-1173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15562032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15562032"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Maria D'Agostino, Marialuisa Sponziello, Cinzia Puppin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Endocrinol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/JME-13-0160"}], "href": "https://doi.org/10.1530/JME-13-0160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24353283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24353283"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Geeta Upadhyay, Rajesh Singh, Gaurav Agarwal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res Treat (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1021321409159"}], "href": "https://doi.org/10.1023/a:1021321409159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12602914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12602914"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Luchuan Li, Bin Lv, Bo Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.04.134"}], "href": "https://doi.org/10.1016/j.bbrc.2015.04.134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25960292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25960292"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Elaine C Morari, Marjory A Marcello, Ana Carolina T Guilhen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Use of sodium iodide symporter expression in differentiated thyroid carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2011.04032.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2011.04032.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21521301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21521301"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Brian Hutzen, Christopher R Pierson, Stephen J Russell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-12-508"}], "href": "https://doi.org/10.1186/1471-2407-12-508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23134812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23134812"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ana Karina M B Sodré, Ileana G S Rubio, Ana Luiza R Galrão, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of low sodium-iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2007-0353"}], "href": "https://doi.org/10.1210/jc.2007-0353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18628528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18628528"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Juan P Nicola, Nancy Carrasco, L Mario Amzel "}, {"type": "b", "children": [{"type": "t", "text": "Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms4948"}], "href": "https://doi.org/10.1038/ncomms4948"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24888603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24888603"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Alexander I Damanakis, Sabine Eckhardt, Annette Wunderlich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs let7 expression in thyroid cancer: correlation with their deputed targets HMGA2 and SLC5A5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-016-2138-z"}], "href": "https://doi.org/10.1007/s00432-016-2138-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26960757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26960757"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Ana Luiza Galrão, Rosalinda Y Camargo, Celso U Friguglietti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation of a New Distal Sodium/Iodide Symporter (NIS) enhancer (NDE) is associated with reduced NIS expression in thyroid tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2013-1450"}], "href": "https://doi.org/10.1210/jc.2013-1450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24432988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24432988"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "David Dingli, Elizabeth R Bergert, Zeljko Bajzer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic iodide trapping by tumor cells expressing the thyroidal sodium iodide symporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.09.219"}], "href": "https://doi.org/10.1016/j.bbrc.2004.09.219"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15522214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15522214"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Israa Mohammad Al-Amily, Pontus Dunér, Leif Groop, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The functional impact of G protein-coupled receptor 142 (Gpr142) on pancreatic β-cell in rodent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pflugers Arch (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00424-019-02262-7"}], "href": "https://doi.org/10.1007/s00424-019-02262-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30767071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30767071"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Mia D Reed-Tsur, Antonio De la Vieja, Christopher S Ginter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes congenital I- transport defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2008-0027"}], "href": "https://doi.org/10.1210/en.2008-0027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18339708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18339708"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Taemoon Chung, Hyewon Youn, Chan Joo Yeom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0142984"}], "href": "https://doi.org/10.1371/journal.pone.0142984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26599396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26599396"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Shinji Kosugi, Hiroomi Okamoto, Aiko Tamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel peculiar mutation in the sodium/iodide symporter gene in spanish siblings with iodide transport defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jcem.87.8.8767"}], "href": "https://doi.org/10.1210/jcem.87.8.8767"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12161518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12161518"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Wenjing Li, Juan Pablo Nicola, L Mario Amzel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Asn441 plays a key role in folding and function of the Na+/I- symporter (NIS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.13-229138"}], "href": "https://doi.org/10.1096/fj.13-229138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23650190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23650190"}]}]}]}