Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1, Longhu Middle Ring Road, Jinshui District, Zhengzhou, 450052, Henan, China.
Hum Cell. 2021 Mar;34(2):457-467. doi: 10.1007/s13577-020-00450-7. Epub 2020 Oct 24.
Forkhead box (FOX) proteins have been identified as key transcription factors in diverse biological processes involved in tumor progression. A large number of FOX proteins are implicated in tumorigenesis of papillary thyroid carcinoma (PTC). Here we investigated the role of Forkhead box K1 (FOXK1) in PTC progression. First, we found that FOXK1 was elevated in both PTC tissues (N = 68) and cell lines. Moreover, up-regulated FOXK1 was associated with shorter overall survival of PTC patients. Second, in vitro functional assays showed that FOXK1 promoted progression of PTC. Mechanistically, FOXK1 could bind to the promoter of cysteine-rich angiogenic inducer 61 (CYR61) and regulate connective tissue growth factor (CTGF) expression through CYR61. Notably, over-expression of CTGF weakened suppression of PTC progression induced by FOXK1 knockdown. Finally, in vivo xenotransplant tumor model indicated that knockdown of FOXK1 suppressed PTC growth. In conclusion, our results indicate that FOXK1 exerts oncogenic roles in PTC via CYR61/CTGF axis, which suggests FOXK1 might act as a potential therapeutic target.
叉头框（FOX）蛋白已被鉴定为参与肿瘤进展的多种生物学过程中的关键转录因子。大量 FOX 蛋白参与甲状腺乳头状癌（PTC）的发生。在这里，我们研究了叉头框 K1（FOXK1）在 PTC 进展中的作用。首先，我们发现 FOXK1 在 PTC 组织（N=68）和细胞系中均升高。此外，上调的 FOXK1 与 PTC 患者的总生存期较短有关。其次，体外功能测定表明 FOXK1 促进了 PTC 的进展。在机制上，FOXK1 可以与富含半胱氨酸的血管生成诱导因子 61（CYR61）的启动子结合，并通过 CYR61 调节结缔组织生长因子（CTGF）的表达。值得注意的是，CTGF 的过表达削弱了 FOXK1 敲低诱导的 PTC 进展的抑制作用。最后，体内异种移植肿瘤模型表明，FOXK1 敲低抑制了 PTC 的生长。总之，我们的结果表明，FOXK1 通过 CYR61/CTGF 轴在 PTC 中发挥致癌作用，这表明 FOXK1 可能作为一种潜在的治疗靶点。
