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

Autor: Yaqi Gao, Tianhui Zou, Pingping Xu, Yingchao Wang, Yi Jiang, Ying-Xuan Chen, Haoyan Chen, Jie Hong, Jing-Yuan Fang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 35, Iss , Pp 100850- (2023)
Druh dokumentu: article
ISSN: 1476-5586
DOI: 10.1016/j.neo.2022.100850
Popis: 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 m6A-seq and RNA-seq identified m6A-modified IFIT1 mediating F. nucleatum induced PD-L1 upregulation. IFIT1 mRNA was modified with m6A modifications in 3’UTR and the m6A 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 m6A-modified IFIT1 and provided new aspects for understanding F. nucleatum mediated immune escape.
Databáze: Directory of Open Access Journals