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Low dose radiation regulates BRAF-induced thyroid cellular dysfunction and transformation

Title
Low dose radiation regulates BRAF-induced thyroid cellular dysfunction and transformation
Author
이수재
Keywords
Low dose radiation; LDR; Thyroid cancer; Paired-box domain 8; PAX8; miR-330-5p; Thyroglobulin; TG
Issue Date
2019-02
Publisher
BMC
Citation
CELL COMMUNICATION AND SIGNALING, v. 17, Page. 1-13
Abstract
Background: The existence of differentiated thyroid cells is critical to respond radioactive iodide treatment strategy in thyroid cancer, and loss of the differentiated phenotype is a trademark of iodide-refractive thyroid disease. While high-dose therapy has been beneficial to several cancer patients, many studies have indicated this clinical benefit was limited to patients having BRAF mutation. BRAF-targeted paired box gene-8 (PAX8), a thyroid-specific transcription factor, generally dysregulated in BRAF-mutated thyroid cancer. Methods: In this study, thyroid iodine-metabolizing gene levels were detected in BRAF-transformed thyroid cells after low and high dose of ionizing radiation. Also, an mRNA-targeted approach was used to figure out the underlying mechanism of low (0.01Gyx10 or 0.1Gy) and high (2Gy) radiation function on thyroid cancer cells after BRAF(V600E) mutation. Results: Low dose radiation (LDR)-induced PAX8 upregulation restores not only BRAF-suppressive sodium/iodide symporter (NIS) expression, one of the major protein necessary for iodine uptake in healthy thyroid, on plasma membrane but also regulate other thyroid metabolizing genes levels. Importantly, LDR-induced PAX8 results in decreased cellular transformation in BRAF-mutated thyroid cells. Conclusion: The present findings provide evidence that LDR-induced PAX8 acts as an important regulator for suppression of thyroid carcinogenesis through novel STAT3/miR-330-5p pathway in thyroid cancers.
URI
https://biosignaling.biomedcentral.com/articles/10.1186/s12964-019-0322-xhttps://repository.hanyang.ac.kr/handle/20.500.11754/107503
ISSN
1478-811X
DOI
10.1186/s12964-019-0322-x
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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