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.
引用
收藏
页数：13
相关论文
共 38 条
[11]   Host-microbiota maladaptation in colorectal cancer [J].
Janney, Alina ;
Powrie, Fiona ;
Mann, Elizabeth H. .
NATURE, 2020, 585 (7826) :509-517
[12]   Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability [J].
Johnson, Britney ;
VanBlargan, Laura A. ;
Xu, Wei ;
White, James P. ;
Shan, Chao ;
Shi, Pei-Yong ;
Zhang, Rong ;
Adhikari, Jagat ;
Gross, Michael L. ;
Leung, Daisy W. ;
Diamond, Michael S. ;
Amarasinghe, Gaya K. .
IMMUNITY, 2018, 48 (03) :487-+
[13]   Fusobacterium nucleatum Facilitates Apoptosis, ROS Generation, and Inflammatory Cytokine Production by Activating AKT/MAPK and NF-κB Signaling Pathways in Human Gingival Fibroblasts [J].
Kang, Wenyan ;
Jia, Zhilong ;
Tang, Di ;
Zhang, Zhanwei ;
Gao, Hui ;
He, Kunlun ;
Feng, Qiang .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2019, 2019
[14]   Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment [J].
Kostic, Aleksandar D. ;
Chun, Eunyoung ;
Robertson, Lauren ;
Glickman, Jonathan N. ;
Gallini, Carey Ann ;
Michaud, Monia ;
Clancy, Thomas E. ;
Chung, Daniel C. ;
Lochhead, Paul ;
Hold, Georgina L. ;
El-Omar, Emad M. ;
Brenner, Dean ;
Fuchs, Charles S. ;
Meyerson, Matthew ;
Garrett, Wendy S. .
CELL HOST & MICROBE, 2013, 14 (02) :207-215
[15]   THADA drives Golgi residency and upregulation of PD-L1 in cancer cells and provides promising target for immunotherapy [J].
Li, Chushu ;
Chi, Hao ;
Deng, Shouyan ;
Wang, Huanbin ;
Yao, Han ;
Wang, Yungang ;
Chen, Dawei ;
Guo, Xun ;
Fang, Jing-Yuan ;
He, Fang ;
Xu, Jie .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (08)
[16]   Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis [J].
Liu, Gao ;
Sun, Jian ;
Yang, Zhang-Fu ;
Zhou, Cheng ;
Zhou, Pei-Yun ;
Guan, Ruo-Yu ;
Sun, Bao-Ye ;
Wang, Zhu-Tao ;
Zhou, Jian ;
Fan, Jia ;
Qiu, Shuang-Jian ;
Yi, Yong .
CELL DEATH & DISEASE, 2021, 12 (03)
[17]   N6-methyladenosine-modified circIGF2BP3 inhibits CD8+ T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer [J].
Liu, Zhenchuan ;
Wang, Tingting ;
She, Yunlang ;
Wu, Kaiqing ;
Gu, Shaorui ;
Li, Lei ;
Dong, Chenglai ;
Chen, Chang ;
Zhou, Yongxin .
MOLECULAR CANCER, 2021, 20 (01)
[18]   Association of Dietary Patterns With Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue [J].
Mehta, Raaj S. ;
Nishihara, Reiko ;
Cao, Yin ;
Song, Mingyang ;
Mima, Kosuke ;
Qian, Zhi Rong ;
Nowak, Jonathan A. ;
Kosumi, Keisuke ;
Hamada, Tsuyoshi ;
Masugi, Yohei ;
Bullman, Susan ;
Drew, David A. ;
Kostic, Aleksandar D. ;
Fung, Teresa T. ;
Garrett, Wendy S. ;
Huttenhower, Curtis ;
Wu, Kana ;
Meyerhardt, Jeffrey A. ;
Zhang, Xuehong ;
Willett, Walter C. ;
Giovannucci, Edward L. ;
Fuchs, Charles S. ;
Chan, Andrew T. ;
Ogino, Shuji .
JAMA ONCOLOGY, 2017, 3 (07) :921-927
[19]   Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis [J].
Mima, Kosuke ;
Nishihara, Reiko ;
Qian, Zhi Rong ;
Cao, Yin ;
Sukawa, Yasutaka ;
Nowak, Jonathan A. ;
Yang, Juhong ;
Dou, Ruoxu ;
Masugi, Yohei ;
Song, Mingyang ;
Kostic, Aleksandar D. ;
Giannakis, Marios ;
Bullman, Susan ;
Milner, Danny A. ;
Baba, Hideo ;
Giovannucci, Edward L. ;
Garraway, Levi A. ;
Freeman, Gordon J. ;
Dranoff, Glenn ;
Garrett, Wendy S. ;
Huttenhower, Curtis ;
Meyerson, Matthew ;
Meyerhardt, Jeffrey A. ;
Chan, Andrew T. ;
Fuchs, Charles S. ;
Ogino, Shuji .
GUT, 2016, 65 (12) :1973-1980
[20]   Fusobacterium nucleatum and T Cells in Colorectal Carcinoma [J].
Mima, Kosuke ;
Sukawa, Yasutaka ;
Nishihara, Reiko ;
Qian, Zhi Rong ;
Yamauchi, Mai ;
Inamura, Kentaro ;
Kim, Sun A. ;
Masuda, Atsuhiro ;
Nowak, Jonathan A. ;
Nosho, Katsuhiko ;
Kostic, Aleksandar D. ;
Giannakis, Marios ;
Watanabe, Hideo ;
Bullman, Susan ;
Milner, Danny A. ;
Harris, Curtis C. ;
Giovannucci, Edward ;
Garraway, Levi A. ;
Freeman, Gordon J. ;
Dranoff, Glenn ;
Chan, Andrew T. ;
Garrett, Wendy S. ;
Huttenhower, Curtis ;
Fuchs, Charles S. ;
Ogino, Shuji .
JAMA ONCOLOGY, 2015, 1 (05) :653-661
1234