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

Cited 2 time in Web of Science Cited 3 time in Scopus
Authors
Kaushik, Neha; Kim, Min-Jung; Kaushik, Nagendra Kumar; Myung, Jae Kyung; Choi, Mi-Young; Kang, Jae-Hyeok; Cha, Hyuk-Jin; Kim, Cha-Soon; Nam, Seon-Young; Lee, Su-Jae
Issue Date
2019-02-13
Publisher
BioMed Central
Citation
Cell Communication and Signaling. 2019 Feb 13;17(1):12
Keywords
Low dose radiationLDRThyroid cancerPaired-box domain 8PAX8miR-330-5pThyroglobulinTG
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 BRAFV600E 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.
ISSN
1478-811X
Language
English
URI
https://hdl.handle.net/10371/147181
DOI
https://doi.org/10.1186/s12964-019-0322-x
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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