Fig. 7: YTHDF1/RNF7/p27 axis promotes prostate cancer progression.

YTHDF1 is highly expressed in prostate cancer, and its high expression correlates with poorer clinical outcome. YTHDF1 increases tumor cell proliferation, migration, and xenograft tumor formation abilities via inducing p27 protein stabilities depending on proteosome degradation signaling. Candidate p27-targeting E3 ubiquitin ligases screening identified RNF7 as the direct downstream target for YTHDF1 in an m6A-dependent manner. The subsequent high translation of RNF7 results in the efficient degradation of the cell cycle inhibitor p27 and malignant tumor cell growth. In addition, YTHDF1 or RNF7 increased the sensitivity to chemotherapy drug cisplatin (DDP) by inducing cellular apoptosis. Most importantly, neddylation inhibitor MLN4924 repressed PCa progression both in vitro and in vivo.