Deubiquitinating Enzyme MINDY1 Facilitates Immune Escape in Breast Cancer by Maintaining the Stability of Immune Checkpoint Protein PD-L1.

Featured with frequent recurrence and distant metastasis, the mortality of breast cancer (BC) increased year by year in recent decades. MINDY lysine 48 deubiquitinase 1 (MINDY1) played an oncogenic role in several tumors. The role of MINDY1 deserved further study in BC. A wide ranges of assays including qRT-PCR, Western blotting, CCK-8 flow cytometry analysis, co-immunoprecipitation assay, Pearson's coefficient tests, and tumor xenograft assay were designed and carried out to determine the role of MINDY1 in BC. Both MINDY1 and programmed death-ligand 1 (PD-L1) is upregulated in BC tissues and cells. In addition, knockdown of MINDY1 attenuated cell viability and promoted the activation of T cells. Mechanistically, MINDY1 stabilized PD-L1 protein by interacting with PD-L1 in BC cells, and MINDY1 is positively associated with PD-L1 in BC tissues. Moreover, rescue assay revealed that the effect of MINDY1 silencing on cell viability and T cell activation was reversed by PD-L1 overexpression. The in vivo study also demonstrated that the effect of MINDY1 knockdown on tumor growth induced by was counteracted by PD-L1 overexpression.In conclusion, we identified PD-L1 as a novel target of MINDY1 and established a significant association between MINDY1 and the cancer immune response. Importantly, our findings reveal that MINDY1 promoted BC progression via PD-L1-mediated immune evasion.