Low dose radiation regulates BRAF-induced thyroid cellular dysfunction and transformation
- 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
- BioMed Central
- Cell Communication and Signaling. 2019 Feb 13;17(1):12
- Low dose radiation; LDR; Thyroid cancer; Paired-box domain 8; PAX8; miR-330-5p; Thyroglobulin; TG
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.
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.
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.
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.