Evolutionary Relationships Between Dysregulated Genes in Oral Squamous Cell Carcinoma and Oral Microbiota

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers in the world. Changes in the composition and abundance of oral microbiota are associated with the development and metastasis of OSCC. To elucidate the exact roles of the oral microbiota in OSCC, it is essential to reveal the evolutionary relationships between the dysregulated genes in OSCC progression and the oral microbiota. Thus, we interrogated the microarray and high-throughput sequencing datasets to obtain the transcriptional landscape of OSCC. After identifying differentially expressed genes (DEGs) with three different methods, pathway and functional analyses were also performed. A total of 127 genes were identified as common DEGs, which were enriched in extracellular matrix organization and cytokine related pathways. Furthermore, we established a predictive pipeline for detecting the coevolutionary of dysregulated host genes and microbial proteomes based on the homology method, and this pipeline was employed to analyze the evolutionary relations between the seven most dysregulated genes (MMP13, MMP7, MMP1, CXCL13, CRISPO3, CYP3A4, and CRNN) and microbiota obtained from the eHOMD database. We found that cytochrome P450 3A4 (CYP3A4), a member of the cytochrome P450 family of oxidizing enzymes, was associated with 45 microbes from the eHOMD database and involved in the oral habitat of Comamonas testosteroni and Arachnia rubra. The peptidase M10 family of matrix metalloproteinases (MMP13, MMP7, and MMP1) was associated with Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Streptococcus salivarius, Tannerella sp._HMT_286, and Streptococcus infantis in the oral cavity. Overall, this study revealed the dysregulated genes in OSCC and explored their evolutionary relationship with oral microbiota, which provides new insight for exploring the microbiota–host interactions in diseases.

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…In summary, F. nucleatum and P. gingivalis exasperate EMT in OSCC cells, further reducing the levels of E-cadherin and dramatically increasing those of MMPs [69,72].…”

“…Briefly, IL-1, IL-6, IL-8, TNF, EGF, and TGF-β trigger intracellular signaling pathways such as the Wingless-related integration site (Wnt)/β catenin, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and the mitogen-activated protein kinases (MAPK)/extracellular regulated kinases (ERK) [65,67]. This leads to the activation of transcription factors such as NF-kB, zinc finger snail homolog (SNAI), basic helix-loop-helix twist homolog (TWIST), and zinc finger E-box binding homeobox (ZEB) [65,[67][68][69]. These transcription factors, in turn, promote the expression of mesenchymal proteins (e.g., vimentin or neuronal cadherin) and pro-invasive proteolytic enzymes, while repressing the expression of epithelial markers such as epithelial (E)-cadherin [65,[67][68][69].…”

“…This leads to the activation of transcription factors such as NF-kB, zinc finger snail homolog (SNAI), basic helix-loop-helix twist homolog (TWIST), and zinc finger E-box binding homeobox (ZEB) [65,[67][68][69]. These transcription factors, in turn, promote the expression of mesenchymal proteins (e.g., vimentin or neuronal cadherin) and pro-invasive proteolytic enzymes, while repressing the expression of epithelial markers such as epithelial (E)-cadherin [65,[67][68][69].…”