YTHDC1 Promoted Cell Proliferation and Decidualization by Maintaining Nuclear C/EBPβ Stability in Decidual Stromal Cells.

Abstract

m6A modification has been shown to play a role in regulating female reproductive diseases. The YT521-B homology (YTH) domain family, including the m6A readers YTHDC1 and YTHDC2, is associated with decidualization during pregnancy. This study aimed to investigate the role of YTHDC1/2-regulated m6A modification in decidualization of endometrial stromal cells (ESCs). We found that YTHDC1 and YTHDC2 were highly expressed in decidual tissues from normal pregnancies. Knockdown of YTHDC1 suppressed cell proliferation and decidualization marker expression in decidual stromal cells (DSCs), whereas overexpression of YTHDC1 enhanced these processes. Mechanistically, YTHDC1 interacted with C/EBPβ via m6A modification and targeted its 3'UTR region. Knockdown of YTHDC1 accelerated the degradation of nuclear C/EBPβ mRNA in DSCs but had minimal effect on cytoplasmic C/EBPβ. Overexpression of C/EBPβ partially rescued the shYTHDC1-induced suppression of cell proliferation and decidualization markers. These results demonstrate that YTHDC1 promotes decidualization and proliferation in DSCs by stabilizing nuclear C/EBPβ mRNA through m6A modification, suggesting a novel therapeutic target for decidualization-related reproductive disorders.