PDF(Pubmed)
Abstract：
Multiple Endocrine Neoplasia 1 gene (MEN1), which is known to be a tumor suppressor gene in lung tissues, encodes a 610 amino acid protein menin. Previous research has proven that MEN1 deficiency promotes the malignant progression of lung cancer. However, the biological role of this gene in the immune microenvironment of lung cancer remains unclear. In this study, we found that programmed cell death-ligand 1 (PD-L1) is upregulated in lung-specific KrasG12D mutation-induced lung adenocarcinoma in mice, after Men1 deficiency. Simultaneously, CD8+ and CD3+ T cells are depleted, and their cytotoxic effects are suppressed. In vitro, PD-L1 is inhibited by the overexpression of menin. Mechanistically, we found that MEN1 inactivation promotes the deubiquitinating activity of COP9 signalosome subunit 5 (CSN5) and subsequently increases the level of PD-L1.
摘要：
多发性内分泌肿瘤1基因(MEN1),已知是肺组织中的肿瘤抑制基因，编码610个氨基酸的menin蛋白。先前的研究已经证明MEN1缺乏促进肺癌的恶性进展。然而,该基因在肺癌免疫微环境中的生物学作用尚不清楚。在这项研究中,我们发现程序性细胞死亡配体1（PD-L1）在肺特异性KrasG12D突变诱导的小鼠肺腺癌中上调，在Men1缺乏后。同时,CD8+和CD3+T细胞耗尽，并且它们的细胞毒性作用被抑制。体外，PD-L1被menin的过表达抑制。机械上,我们发现MEN1失活促进COP9信号体亚基5(CSN5)的去泛素化活性,并随后增加PD-L1的水平.
