Caspase recruitment domain and
membrane-associated guanylate kinase-like domain protein 3 (CARMA3) was reported as an
oncoprotein overexpressed in several
cancers. The expression pattern of CARMA3 and its clinical significance in human
bladder cancer have not been well characterized. In the present study, CARMA3 expression was analyzed in 90 archived
bladder cancer specimens using immunohistochemistry, and the correlation between CARMA3 expression and clinicopathological parameters was evaluated. We found that CARMA3 was overexpressed in 35 of 90 (38.8%)
bladder cancer specimens. Significant association was observed between CARMA3 overexpression with
tumor status (p = 0.081) and
tumor grade (p = 0.027). To further explore the
biological functions of CARMA3 in
bladder cancer, we depleted CARMA3 in T24 and 5637 cell lines using
small interfering RNA (
siRNA). Using cell counting kit-8 (CCK8) assay and colony formation assay, we were able to show that CARMA3 depletion inhibited cell proliferation and colony number. Further study demonstrated that CARMA3 depletion decreased an expression of
nuclear factor kappa B (NF-κB) targets
cyclin D1 and Bcl-2 expression, as well as IκB phosphorylation.
Luciferase reporter assay showed that CARMA3 depletion could downregulate NF-κB reporter activity. In conclusion, CARMA3 is overexpressed in
bladder cancer and regulates malignant cell growth and NF-κB signaling, which makes CARMA3 a candidate therapeutic target for
bladder cancer.