TAF1D promotes tumorigenesis and metastasis by activating PI3K/AKT/mTOR signaling in clear cell renal cell carcinoma

Abstract

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 0 /G 1 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. • This article unveils the role of TAF1D in ccRCC for the first time. • TAF1D promotes ccRCC proliferation and metastasis in vivo and in vitro. • TAF1D influences the cell cycle and EMT through the PI3K/AKT/mTOR pathway. • TAF1D Knockdown of TAF1D enhances ccRCC sensitivity to sunitinib. • TAF1D promises to be a new target for treating ccRCC and overcoming TKI resistance.