SBP1 promotes tumorigenesis of thyroid cancer through TXN/NIS pathway.

Autor: Ma J; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China., Huang X; Department of General Surgery, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China., Xu J; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China., Li Z; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China., Lai J; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China., Shen Y; Department of General Surgery, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China., Zhao J; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China., Sun X; Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China. sunxy@mail.xjtu.edu.cn., Ma L; Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China.
Jazyk: angličtina
Zdroj: Molecular medicine (Cambridge, Mass.) [Mol Med] 2023 Sep 08; Vol. 29 (1), pp. 121. Date of Electronic Publication: 2023 Sep 08.
DOI: 10.1186/s10020-023-00700-y
Abstrakt: Background: As the tissue with the highest selenium content in the body, the occurrence and development of thyroid cancer are closely related to selenium and selenoproteins. Selenium-binding protein 1 (SBP1) has been repeatedly implicated in several cancers, but its role and molecular mechanisms in thyroid cancer remains largely undefined.
Methods: The expression of SBP1, sodium/iodide symporter (NIS) and thioredoxin (TXN) were analyzed in clinical samples and cell lines. Cell counting kit-8 (CCK-8) and tube formation assays were used to analyze the cell viability and tube formation of cells. Immunofluorescence was used to determine the expression of the NIS. Co-immunoprecipitation (Co-IP) assay was carried out to verify the interaction of SBP1 with TXN. The mouse xenograft experiment was performed to investigate the growth of thyroid cancer cells with SBP1 knockdown in vivo.
Results: SBP1 was significantly increased in human thyroid cancer tissues and cells, especially in anaplastic thyroid cancer. Overexpression of SBP1 promoted FTC-133 cell proliferation, and the culture supernatant of SBP1-overexpression FTC-133 cells promoted tube formation of human retinal microvascular endothelial cells. Knockdown of SBP1, however, inhibited cell proliferation and tube formation. Furthermore, overexpression of SBP1 inhibited cellular differentiation of differentiated thyroid cancer cell line FTC-133, as indicated by decreased expression of thyroid stimulating hormone receptors, thyroglobulin and NIS. Knockdown of SBP1, however, promoted differentiation of BHT101 cells, an anaplastic thyroid cancer cell line. Notably, TXN, a negative regulator of NIS, was found to be significantly upregulated in human thyroid cancer tissues, and it was positively regulated by SBP1. Co-IP assay implied a direct interaction of SBP1 with TXN. Additionally, TXN overexpression reversed the effect of SBP1 knockdown on BHT101 cell viability, tube formation and cell differentiation. An in vivo study found that knockdown of SBP1 promoted the expression of thyroid stimulating hormone receptors, thyroglobulin and NIS, as well as inhibited the growth and progression of thyroid cancer tumors.
Conclusion: SBP1 promoted tumorigenesis and dedifferentiation of thyroid cancer through positively regulating TXN.
(© 2023. The Feinstein Institute for Medical Research.)
Databáze: MEDLINE
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