Exploring the interplay between Fusobacterium nucleatum with the expression of microRNA, and inflammatory mediators in colorectal cancer

Narjess Bostanghadiri; Shabnam Razavi; Aref Shariati; Malihe Talebi; Shiva Mirkalantari; Amirnader Emami Razavi; Davood Darban-Sarokhalil

doi:10.3389/fmicb.2023.1302719

Exploring the interplay between Fusobacterium nucleatum with the expression of microRNA, and inflammatory mediators in colorectal cancer

Front Microbiol. 2023 Nov 23:14:1302719. doi: 10.3389/fmicb.2023.1302719. eCollection 2023.

Authors

Narjess Bostanghadiri¹, Shabnam Razavi^{1

2}, Aref Shariati³, Malihe Talebi¹, Shiva Mirkalantari¹, Amirnader Emami Razavi⁴, Davood Darban-Sarokhalil¹

Affiliations

¹ Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
² Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
³ Department of Medical Laboratory Sciences, Khomein University of Medical Sciences, Khomeyn, Iran.
⁴ Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Background: Fusobacterium nucleatum has been recognized as an important key bacterium in the cause and spread of colorectal carcinogenesis. Nevertheless, the clinical relevance of F. nucleatum in colorectal cancer (CRC) and its effect on immune factors and the tumor microenvironment have not been fully elucidated.

Materials and methods: The frequency of F. nucleatum was measured in 100 paired tumor and normal tissue specimens by TaqMan quantification Real-Time Polymerase Chain Reaction (qPCR). The mRNA expression levels of cytokines (IL-6, IL-10, IL-12β, IL-17, TNF-α, TLR-2, and TLR-4), and miRNAs (miR-21, miR-31) were examined. Eventually, any potential correlations between the molecular and clinicopathological features of the neoplastic samples and the abundance of F. nucleatum were analyzed.

Results: The relative frequency of F. nucleatum was significantly increased in cancerous tissue compared to adjacent non-tumor tissues. Furthermore, the high level of F. nucleatum was significantly associated with histological grade III and IV CRC tissues (P = 0.027 and P = 0.022, respectively) and perineural invasion-positive patients (P = 0.037). In addition, the expression levels of IL-6, IL-17, TNF-α,IL-12β, TLR-2, and TLR-4 as well as miR-21 and miR-31 showed a significant increase in the cancer group. A notable correlation was also observed between the high status of F. nucleatum and the expression of IL-6, TNF-α and miR-21.

Conclusion: Our results emphasize the importance of F. nucleatum and changes in the expression of genes involved in CRC. Studying the microbial profile and gene expression changes in CRC patients may be a promising approach to improve screening methods and provide therapeutic strategies.

Keywords: Fusobacterium nucleatum; colorectal cancer; cytokines; miR-21; miR-31.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by grant no: 1400-2-4-21695 from the Iran University of Medical Sciences.