Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis

Bladder cancer (BLCA) is a common malignant tumor of the urinary system, with significant morbidity and mortality rates worldwide. The <i>MEN1</i> gene, encoding the menin protein, plays a regulatory role in several cancers. However, the role played by menin in BLCA remains elusive. In this study, our data demonstrated that the expression of menin was significantly up-regulated in BLCA tissues versus normal tissues, and the high expression of menin was strongly correlated with poor prognosis of BLCA patients. <i>In vitro</i>, silencing <i>MEN1</i> inhibited cell proliferation and induced cell cycle arrest at the G1/S phase in BLCA cells. Furthermore, RNA sequencing analysis revealed that <i>MEN1</i> knockdown significantly inhibited the Wnt/β-catenin signaling in BLCA cells. Meanwhile, we further confirmed that β-catenin served as a critical downstream effector of menin in BLCA cells. Mechanically, chromatin immunoprecipitation analysis demonstrated that menin promoted <i>CTNNB1</i> (catenin beta 1) transcription through binding to the <i>CTNNB1</i> proximal promoter in BLCA cells. Interestingly, menin collaborated with TFAP2C, a regulator of β-catenin in BLCA cells, to enhance the transcription of the <i>CTNNB1</i> gene. More intriguingly, BAY-155, a menin molecule inhibitor, inhibited cell growth of BLCA cells both <i>in vitro</i> and <i>in vivo</i> by suppressing the expression of menin, TFAP2C, and β-catenin. Our current work unveils an important role of the menin in triggering the TFAP2C/β-catenin axis, which contributes to cell proliferation of BLCA cells. Therefore, menin might be served as a new therapeutic target for BLCA.