Mediator complex subunit 8 promotes bladder cancer progression via Stearoyl-CoA desaturase.

Mediator complex subunits have recently been reported to be associated with tumor progression, the tumor immune microenvironment, and therapeutic responses. However, limited research about oncology has been conducted on Mediator complex subunit 8 (MED8). The functional role and molecular mechanism of MED8 in bladder cancer (BLCA) require further systematic bioinformatic analysis and experimental validation. Analysis of The Cancer Genome Atlas pan-cancer cohort and multiple bladder cancer datasets revealed MED8 upregulation in various tumors. More importantly, MED8 expression was correlated with poor prognosis in bladder cancer patients. In vitro proliferation and migration assays demonstrated that MED8 knockdown suppressed bladder cancer cell proliferation and motility. Conversely, MED8 overexpression promoted cellular proliferation and migration. Meanwhile, the influence of MED8 on the growth of BLCA was validated in vivo. Integrated multi-omics sequencing (RNA-seq combined with Astral-DIA proteomics) identified Stearoyl-CoA desaturase (SCD) as a potential downstream effector of MED8. Finally, rescue experiments confirmed that MED8 regulates bladder cancer cell proliferation and migration through SCD. In conclusion, this study is the first to reveal the oncogenic function and overexpression of MED8 in bladder cancer and its tumor-promoting effects are mediated through SCD regulation. These findings provide novel insights into the molecular mechanisms of bladder cancer progression and establish a theoretical foundation for targeting MED8 as a therapeutic strategy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-026-06083-7.