Low dose radiation regulates BRAF-induced thyroid cellular dysfunction and transformationopen access
- 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
- Feb-2019
- Publisher
- BMC
- Keywords
- Low dose radiation; LDR; Thyroid cancer; Paired-box domain 8; PAX8; miR-330-5p; Thyroglobulin; TG
- Citation
- CELL COMMUNICATION AND SIGNALING, v.17, no.1, pp.1 - 13
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL COMMUNICATION AND SIGNALING
- Volume
- 17
- Number
- 1
- Start Page
- 1
- End Page
- 13
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/15076
- DOI
- 10.1186/s12964-019-0322-x
- ISSN
- 1478-811X
- 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.
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