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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