Yang Feibiao, Xiao Zhangsheng, Zhang Songze
Department of Thyroid and Breast Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China.
Exp Ther Med. 2022 Jun;23(6):434. doi: 10.3892/etm.2022.11361. Epub 2022 May 9.
The transcription factor, forkhead box P2 (FOXP2) has tumor-suppressive effects in several types of cancer. However, the regulatory role and underlying mechanism of FOXP2 in thyroid cancer (THCA) is not completely understood. In the present study, the mRNA expression levels of FOXP2 and ribosomal protein S6 kinase A6 (RPS6KA6) were evaluated using the GEPIA database and THCA cell lines. The association between FOXP2 and RPS6KA6 was analyzed using the LinkedOmics, and GEPIA databases. Then, the binding sites of FOXP2 and the RPS6KA6 promotor was predicted using the JASPAR database, and verified using a dual-luciferase reporter assay and chromatin immunoprecipitation. In addition, functional assays investigating FOXP2 and RPS6KA6 were conducted in the TPC-1 cell line. The data showed that FOXP2 and RPS6KA6 mRNA expression levels were decreased in the THCA tissues, and cell lines. Overexpression of FOXP2 inhibited cell proliferation and promoted apoptosis in the THCA cell lines. Furthermore, RPS6KA6 mRNA expression levels were reduced in THCA and were correlated with FOXP2 expression level. Mechanistic studies revealed that FOXP2 binds directly to the promotor region of RPS6KA6 and modulated the expression level of RPS6KA6 transcriptionally. In addition, rescue experiments showed that knockdown of RPS6KA6 expression reversed the effects of FOXP2 overexpression on THCA cell proliferation and apoptosis, and the regulation of FOXP2/RPS6KA6 may be associated with the PI3K/AKT pathway. In summary, FOXP2 was associated with the proliferation and apoptosis of human THCA cells via the transcriptional activation of RPS6KA6. The FOXP2/RPS6KA6 axis could be a promising target for the treatment of THCA.
转录因子叉头框蛋白P2（FOXP2）在多种癌症中具有肿瘤抑制作用。然而，FOXP2在甲状腺癌（THCA）中的调控作用及潜在机制尚未完全明确。在本研究中，利用GEPIA数据库和THCA细胞系评估了FOXP2和核糖体蛋白S6激酶A6（RPS6KA6）的mRNA表达水平。使用LinkedOmics和GEPIA数据库分析了FOXP2与RPS6KA6之间的关联。然后，使用JASPAR数据库预测FOXP2与RPS6KA6启动子的结合位点，并通过双荧光素酶报告基因检测和染色质免疫沉淀进行验证。此外，在TPC-1细胞系中进行了研究FOXP2和RPS6KA6的功能实验。数据显示，THCA组织和细胞系中FOXP2和RPS6KA6的mRNA表达水平降低。FOXP2的过表达抑制了THCA细胞系中的细胞增殖并促进了细胞凋亡。此外，THCA中RPS6KA6的mRNA表达水平降低，且与FOXP2表达水平相关。机制研究表明，FOXP2直接与RPS6KA6的启动子区域结合，并在转录水平上调节RPS6KA6的表达水平。此外，拯救实验表明，敲低RPS6KA6表达可逆转FOXP2过表达对THCA细胞增殖和凋亡的影响，且FOXP2/RPS6KA6的调控可能与PI3K/AKT信号通路有关。总之，FOXP2通过RPS6KA6的转录激活与人THCA细胞的增殖和凋亡相关。FOXP2/RPS6KA6轴可能是THCA治疗的一个有前景的靶点。
