Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Cell Signal. 2024 Dec;124:111425. doi: 10.1016/j.cellsig.2024.111425. Epub 2024 Sep 20.
Clear cell renal cell carcinoma (ccRCC) is a malignant tumor needs more effective treatments. TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D) is a member of the selective factor 1 complex and functions in RNA polymerase I-dependent transcription. Higher TAF1D expression was found in ccRCC tumor tissues and indicated worse survival. Our study aimed to investigate the therapeutic potential of TAF1D in ccRCC. The proliferation and migration of ccRCC cells were significantly inhibited after TAF1D knockdown, while TAF1D overexpressing had opposite effects. Moreover, TAF1D knockdown induced cells to undergo G/G cell cycle arrest and blockade of the epithelial-mesenchymal transition (EMT) process. Mechanistically, TAF1D affect the cell cycle and EMT through the PI3K/AKT/mTOR signaling pathway, thereby promoting the proliferation and metastasis of ccRCC cells in vivo and in vitro. The inhibitory effect of TAF1D knockdown could be reverted by the AKT activator SC79 in ccRCC cells, confirming this mechanism. Besides, TAF1D knockdown in ccRCC cells had a sensitizing effect on sunitinib and enhanced tumor cell inhibiting induced by sunitinib. In conclusion, TAF1D may be a promising target for the treatment of ccRCC and for overcoming sunitinib resistance.
透明细胞肾细胞癌（ccRCC）是一种恶性肿瘤，需要更有效的治疗方法。TATA 框结合蛋白相关因子 RNA 聚合酶 I 亚基 D（TAF1D）是选择性因子 1 复合物的成员，在 RNA 聚合酶 I 依赖性转录中发挥作用。在 ccRCC 肿瘤组织中发现 TAF1D 表达较高，提示预后较差。我们的研究旨在探讨 TAF1D 在 ccRCC 中的治疗潜力。TAF1D 敲低后，ccRCC 细胞的增殖和迁移明显受到抑制，而 TAF1D 过表达则产生相反的效果。此外，TAF1D 敲低诱导细胞发生 G1/G0 细胞周期阻滞并阻断上皮-间充质转化（EMT）过程。机制上，TAF1D 通过 PI3K/AKT/mTOR 信号通路影响细胞周期和 EMT，从而促进 ccRCC 细胞在体内和体外的增殖和转移。在 ccRCC 细胞中，AKT 激活剂 SC79 可逆转 TAF1D 敲低的抑制作用，证实了这一机制。此外，ccRCC 细胞中 TAF1D 的敲低对舒尼替尼具有增敏作用，并增强了舒尼替尼诱导的肿瘤细胞抑制作用。总之，TAF1D 可能是治疗 ccRCC 和克服舒尼替尼耐药的有前途的靶点。
