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

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

Liang Ren,^1,2 Li Wang,² Zhewei Cao,³ Xuelin Yi,⁴ Yiran Chen,² Yang Yang⁵ and Ya Liu²

¹Tianjin University, Tianjin, China
²Department of Ultrasound Medicine, Yiling People’s Hospital, Yichang, China
³Department of Pharmacy, Yiling People’s Hospital, Yichang, China
⁴Department of Science and Education, Yiling People’s Hospital, Yichang, China
⁵Department of Pediatrics, Yiling People’s Hospital, Yichang, China

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.

Key words —— breast cancer; immune escape; MINDY lysine 48 deubiquitinase 1; PD-L1

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Tohoku J. Exp. Med., 2025 May, 266(3), 237-246.

Correspondence: Ya Liu, Yiling People’s Hospital, No.32, Donghu Avenue, Xiaoxita Street, Yiling District, Yichang City, Hubei Province, China.

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