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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.

Author information

Kaushik N1, Kim MJ2, Kaushik NK3, Myung JK4, Choi MY1, Kang JH1, Cha HJ5, Kim CS6, Nam SY7, Lee SJ8,9.
1
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.
2
Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
3
Plasma Bioscience Research Center, Applied Plasma Medicine Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 01897, Republic of Korea.
4
Department of Radiation Pathology, Korea Cancer Center Hospital, Seoul, South Korea.
5
College of Pharmacy, Seoul National University, Seoul, South Korea.
6
Department of Preventive Medicine, College of Medicine, Dongguk University, Gyeongju, 38066, Korea.
7
Radiation Health Institute, Korea Hydro and Nuclear Power Co. Ltd, Seoul, South Korea. namsy6660@khnp.co.kr.
8
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea. sj0420@hanyang.ac.kr.
9
Laboratory of Molecular Biochemistry, Department of Life Science, Hanyang University, 17 Haengdang-Dong, Seongdong-Ku, Seoul, 04763, South Korea. sj0420@hanyang.ac.kr.