Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer

被引：35
作者：
Gao, Yaqi [1 ,2 ]
Zou, Tianhui [1 ,2 ]
Xu, Pingping [1 ,2 ]
Wang, Yingchao [1 ,2 ]
Jiang, Yi [1 ,2 ]
Chen, Ying-Xuan [1 ,2 ]
Chen, Haoyan [1 ,2 ]
Hong, Jie [1 ,2 ]
Fang, Jing-Yuan [1 ,2 ]
机构：
[1] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Div Gastroenterol & Hepatol, Shanghai, Peoples R China
来源：
NEOPLASIA | 2023年 / 35卷
基金：
中国国家自然科学基金;
关键词：
F.nucleatum; Colorectal cancer; m(6)A; IFIT1; PD-L1; MICROBIOTA;
D O I：
10.1016/j.neo.2022.100850
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Fusobacterium nucleatum ( F. nucleatum) is enriched in colorectal cancer (CRC) tissues and a high amount of F. nucleatum was associated with an immunosuppressive tumor environment. PD-L1 is an important immune checkpoint expressed on tumor cells and promotes tumor immune escape. Whether PD-L1 is regulated by F. nucleatum is still unclear. We demonstrated that F. nucleatum promoted CRC progression and upregulated PD-L1 protein expression in CRC cell lines. Combined m(6)A-seq and RNA-seq identified m(6)A-modified IFIT1 mediating F. nucleatum induced PD-L1 upregulation. IFIT1 mRNA was modified with m6A modifications in 3'UTR and the m(6)A levels were altered by F. nucleatum treatment. Our results also indicated that IFIT1 served as a potential oncogene in CRC and regulated PD-L1 protein levels through altering PD-L1 ubiquitination. Clinical CRC data confirmed the correlation among F. nucleatum abundance, IFIT1 and PD-L1 expressions. Our work highlighted the function of F. nucleatum in stimulating PD-L1 expression through m(6)A-modified IFIT1 and provided new aspects for understanding F. nucleatum mediated immune escape.
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页数：13
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