{Reference Type}: Journal Article
{Title}: Membrane-associated RING-CH 7 inhibits stem-like capacities of bladder cancer cells by interacting with nucleotide-binding oligomerization domain containing 1.
{Author}: Zhuang J;Zhang L;Zhang S;Zhang Z;Xie T;Zhao W;Liu Y;
{Journal}: Cell Biosci
{Volume}: 14
{Issue}: 1
{Year}: 2024 Mar 10
{Factor}: 9.584
{DOI}: 10.1186/s13578-024-01210-y
{Abstract}: <B>BACKGROUND: </B>Cancer stem-like capacities are major factors contributing to unfavorable prognosis. However, the associated molecular mechanisms underlying cancer stem-like cells (CSCs) maintain remain unclear. This study aimed to investigate the role of the ubiquitin E3 ligase membrane-associated RING-CH 7 (MARCH7) in bladder cancer cell CSCs.<BR><B>METHODS: </B>Male BALB/c nude mice aged 4-5 weeks were utilized to generate bladder xenograft model. The expression levels of MARCHs were checked in online databases and our collected bladder tumors by quantitative real-time PCR (q-PCR) and immunohistochemistry (IHC). Next, we evaluated the stem-like capacities of bladder cancer cells with knockdown or overexpression of MARCH7 by assessing their spheroid-forming ability and spheroid size. Additionally, we conducted proliferation, colony formation, and transwell assays to validate the effects of MARCH7 on bladder cancer CSCs. The detailed molecular mechanism of MARCH7/NOD1 was validated by immunoprecipitation, dual luciferase, and in vitro ubiquitination assays. Co-immunoprecipitation experiments revealed that nucleotide-binding oligomerization domain-containing 1 (NOD1) is a substrate of MARCH7.<BR><B>RESULTS: </B>We found that MARCH7 interacts with NOD1, leading to the ubiquitin-proteasome degradation of NOD1. Furthermore, our data suggest that NOD1 significantly enhances stem-like capacities such as proliferation and invasion abilities. The overexpressed MARCH7 counteracts the effects of NOD1 on bladder cancer CSCs in both in vivo and in vitro models.<BR><B>CONCLUSIONS: </B>Our findings indicate that MARCH7 functions as a tumor suppressor and inhibits the stem-like capacities of bladder tumor cells by promoting the ubiquitin-proteasome degradation of NOD1. Targeting the MARCH7/NOD1 pathway could be a promising therapeutic strategy for bladder cancer patients.