METTL3 promotes cell cycle progression via m⁶A/YTHDF1-dependent regulation of <i>CDC25B</i> translation

Abstract

The cell cycle machinery controls cell proliferation and the dysregulation of the cell cycle lies at the heart of carcinogenesis. Thus, exploring the unknown regulators involved in the cell cycle not only contribute to better understanding of cell proliferation but also provide substantial improvement to cancer therapy. In this study, we identified that the expression of methyltransferase METTL3 was upregulated in the M phase. Overexpression of METTL3 facilitated cell cycle progression, induced cell proliferation <i>in vitro</i> and enhanced tumorigenicity <i>in vivo</i>, while knockdown of METTL3 reversed these processes. METTL3 induced <i>CDC25B</i> mRNA m⁶A modification in the M phase, which accelerated the translation of <i>CDC25B</i> mRNA through YTHDF1-dependent m⁶A modification. Clinical data analysis showed that METTL3 and CDC25B were highly expressed in cervical cancer. Our work reveals that a new mechanism regulates cell cycle progression through the METTL3/m⁶A/CDC25B pathway, which provides insight into the critical roles of m⁶A methylation in the cell cycle.