Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer

UFM1 对 PLAC8 的修饰通过影响三阴性乳腺癌中的 PD-L1 水平来影响肿瘤增殖和免疫反应

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作者:Misha Mao #, Yongxia Chen #, Jingjing Yang, Yifan Cheng, Ling Xu, Feiyang Ji, Jichun Zhou, Xun Zhang, Zhaoqing Li, Cong Chen, Siwei Ju, Jiahang Zhang, Linbo Wang

Background

Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer.

Conclusions

Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.

Methods

We measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues.

Results

PLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1. Conclusions: Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.

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