Cargando…

Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer

BACKGROUND: Emerging evidence suggests a potential relationship between gut microbiota and the host response to chemotherapeutic drugs including 5-fluorouracil (5-Fu). Fusobacterium nucleatum (Fn) has been linked to the initiation and progression of colorectal cancer (CRC). Unfortunately, little was...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Sheng, Yang, Yongzhi, Weng, Wenhao, Guo, Bomin, Cai, Guoxiang, Ma, Yanlei, Cai, Sanjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327560/
https://www.ncbi.nlm.nih.gov/pubmed/30630498
http://dx.doi.org/10.1186/s13046-018-0985-y
_version_ 1783386493875650560
author Zhang, Sheng
Yang, Yongzhi
Weng, Wenhao
Guo, Bomin
Cai, Guoxiang
Ma, Yanlei
Cai, Sanjun
author_facet Zhang, Sheng
Yang, Yongzhi
Weng, Wenhao
Guo, Bomin
Cai, Guoxiang
Ma, Yanlei
Cai, Sanjun
author_sort Zhang, Sheng
collection PubMed
description BACKGROUND: Emerging evidence suggests a potential relationship between gut microbiota and the host response to chemotherapeutic drugs including 5-fluorouracil (5-Fu). Fusobacterium nucleatum (Fn) has been linked to the initiation and progression of colorectal cancer (CRC). Unfortunately, little was known about the relationship between Fn infection and chemotherapeutic efficacy. Here, we investigate the potential relationship between Fn infection and chemotherapeutic efficacy of 5-Fu in CRC. METHODS: Differentially expressed genes of CRC cell lines induced by Fn infection were analyzed based on a whole genome microarray analysis Then, we explored the relationship between upregulation of BIRC3 induced by Fn infection and chemoresistance to 5-Fu in vitro and in vivo. Furthermore, we dissected the mechanisms involved in Fn-induced BIRC3 expression. Finally, we investigated the clinical relevance of Fn infection, BIRC3 protein expression and chemoresistance to 5-Fu treatment in CRC patients. RESULTS: BIRC3 was the most upregulated gene induced by Fn infection via the TLR4/NF-κB pathway in CRC cells; Fn infection reduced the chemosensitivity of CRC cells to 5-Fu through upregulation of BIRC3 in vitro and in vivo. High Fn abundance correlated with chemoresistance in advanced CRC patients who received standard 5-Fu-based adjuvant chemotherapy after radical surgery. CONCLUSIONS: Our evidence suggests that Fn and BIRC3 may serve as promising therapeutic targets for reducing chemoresistance to 5-Fu treatment in advanced CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0985-y) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6327560
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-63275602019-01-15 Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer Zhang, Sheng Yang, Yongzhi Weng, Wenhao Guo, Bomin Cai, Guoxiang Ma, Yanlei Cai, Sanjun J Exp Clin Cancer Res Research BACKGROUND: Emerging evidence suggests a potential relationship between gut microbiota and the host response to chemotherapeutic drugs including 5-fluorouracil (5-Fu). Fusobacterium nucleatum (Fn) has been linked to the initiation and progression of colorectal cancer (CRC). Unfortunately, little was known about the relationship between Fn infection and chemotherapeutic efficacy. Here, we investigate the potential relationship between Fn infection and chemotherapeutic efficacy of 5-Fu in CRC. METHODS: Differentially expressed genes of CRC cell lines induced by Fn infection were analyzed based on a whole genome microarray analysis Then, we explored the relationship between upregulation of BIRC3 induced by Fn infection and chemoresistance to 5-Fu in vitro and in vivo. Furthermore, we dissected the mechanisms involved in Fn-induced BIRC3 expression. Finally, we investigated the clinical relevance of Fn infection, BIRC3 protein expression and chemoresistance to 5-Fu treatment in CRC patients. RESULTS: BIRC3 was the most upregulated gene induced by Fn infection via the TLR4/NF-κB pathway in CRC cells; Fn infection reduced the chemosensitivity of CRC cells to 5-Fu through upregulation of BIRC3 in vitro and in vivo. High Fn abundance correlated with chemoresistance in advanced CRC patients who received standard 5-Fu-based adjuvant chemotherapy after radical surgery. CONCLUSIONS: Our evidence suggests that Fn and BIRC3 may serve as promising therapeutic targets for reducing chemoresistance to 5-Fu treatment in advanced CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0985-y) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-10 /pmc/articles/PMC6327560/ /pubmed/30630498 http://dx.doi.org/10.1186/s13046-018-0985-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhang, Sheng
Yang, Yongzhi
Weng, Wenhao
Guo, Bomin
Cai, Guoxiang
Ma, Yanlei
Cai, Sanjun
Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer
title Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer
title_full Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer
title_fullStr Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer
title_full_unstemmed Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer
title_short Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer
title_sort fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of birc3 expression in colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327560/
https://www.ncbi.nlm.nih.gov/pubmed/30630498
http://dx.doi.org/10.1186/s13046-018-0985-y
work_keys_str_mv AT zhangsheng fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer
AT yangyongzhi fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer
AT wengwenhao fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer
AT guobomin fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer
AT caiguoxiang fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer
AT mayanlei fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer
AT caisanjun fusobacteriumnucleatumpromoteschemoresistanceto5fluorouracilbyupregulationofbirc3expressionincolorectalcancer