Tripartite Motif Containing 66 Promotes Malignant Progression of Bladder Cancer by Activating Matrix Metallopeptidase 11

Abstract

We aimed to investigate the pivotal role of Tripartite Motif Containing 66 (TRIM66) in bladder cancer (BCa) and elucidate its underlying mechanism in promoting BCa cell metastasis. Tumor and adjacent normal tissues were collected from 62 BCa patients, and TRIM66 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between TRIM66 expression and clinical indicators, as well as patient prognosis, was analyzed. In addition, an in vitro model was established by silencing TRIM66 in a BCa cell line. The impact of TRIM66 on BCa cell invasion and metastasis was evaluated through Transwell and cell wound healing assays. Through meticulous bioinformatics analysis and luciferase assays, we confirmed that TRIM66 specifically binds to Matrix Metallopeptidase 11 (MMP11). Moreover, mRNA expression analysis revealed a positive correlation between TRIM66 and MMP11 in BCa tumor tissues. Intriguingly, in a cell recovery experiment, overexpression of MMP11 reversed the inhibition of migration and proliferation caused by TRIM66 downregulation. Collectively, our findings unequivocally indicate that heightened TRIM66 expression is closely associated with a malignant phenotype in BCa tissues. Silencing TRIM66 significantly mitigates BCa cell metastasis in vitro by downregulating MMP11. These observations shed light on the critical involvement of the TRIM66-MMP11 axis in BCa progression, offering promising avenues for therapeutic interventions targeting this pathway.