MYEOV Facilitates the Progression of Bladder Cancer by Upregulating MMP9 Via the TGF-β-H3K4me3 Epigenetic Axis.

Abstract

Bladder cancer (BC) represents the second most prevalent malignant tumor within the urinary system. Its high rates of recurrence and metastasis contribute to an unfavorable prognosis. The myeloma overexpressed gene (MYEOV) has been associated with the progression of various cancers. However, the specific role and underlying mechanisms of MYEOV in BC progression remain to be elucidated. Our research demonstrates that MYEOV is significantly upregulated in BC and correlates with poor clinical outcomes. Reducing or overexpressing MYEOV can inhibit or promote the proliferation and invasive ability of BC. Mechanistically, MYEOV activates the TGF-β-H3K4me3 signaling pathway to directly modulate MMP9 promoter activity through epigenetic modifications, thereby enhancing MMP9 expression. Notably, the effects of MYEOV knockdown or overexpression on BC proliferation and invasion can be counteracted by restoring MMP9 expression. Furthermore, NSUN2 modulates the stability of MYEOV mRNA via m5C methylation, leading to its increased expression in BC. Collectively, our findings elucidate the role of MYEOV in facilitating BC progression through the regulation of MMP9 in vitro. In conclusion, our findings identified that MYEOV is a novel target in the development of bladder cancer and offer new insights into potential therapeutic strategies.