Time-Course Transcriptome Analysis of Gingiva-Derived Mesenchymal Stem Cells Reveals That Fusobacterium nucleatum Triggers Oncogene Expression in the Process of Cell Differentiation

Abstract

Fusobacterium nucleatum has pathogenic effects on oral squamous cell carcinoma and colon cancer, while the effects of continuously altered gene expression in normal human cells, as induced by persistent exposure to F. nucleatum, remain unclear. In this study, a microarray Significant Profiles (maSigPro) analysis was used to obtain the transcriptome profile of gingiva-derived mesenchymal stem cells (GMSCs) stimulated by F. nucleatum for 3, 7, 14, and 21 day, and the results revealed 790 (nine clusters) differentially expressed genes (DEGs), which were significantly enriched in cell adherens junctions and cancer-related pathways. On the basis of a short time-series expression miner (STEM) analysis, all the expressed genes in the GMSCs were grouped into 50 clusters according to dynamic gene expression patterns, and the expression levels of three gene clusters in the F. nucleatum-treated GMSCs were significantly different than the predicted values. Among the 790 DEGs, 50 tumor-associated genes (TAGs; such as L3MBTL4, CD163, CCCND2, CADM1, BCL7A, and IGF1) and five core dynamic DEGs (PLCG2, CHI3L2, L3MBTL4, SH2D2A, and NLRP3) were identified during F. nucleatum stimulation. Results from a GeneMANIA database analysis showed that PLCG2, CHI3L2, SH2D2A, and NLRP3 and 20 other proteins formed a complex network of which 12 genes were enriched in cancer-related pathways. Based on the five core dynamic DEGs, the related microRNAs (miRNAs) and transcription factors (TFs) were obtained from public resources, and an integrated network composed of the related TFs, miRNAs, and mRNAs was constructed. The results indicated that these genes were regulated by several miRNAs, such as miR-372-3p, miR-603, and miR-495-3p, and several TFs, including CREB3, GATA2, and SOX4. Our study suggests that long-term stimulation by F. nucleatum may trigger the expression of cancer-related genes in normal gingiva-derived stem cells.

Investigating Transcriptional Dynamics Changes and Time-Dependent Marker Gene Expression in the Early Period After Skeletal Muscle Injury in Rats

“…However, there is still a lack of genes or biomarkers that can be used to clearly distinguish the various stages after injury and for monitoring the continuous and dynamic biological processes. Using next-generation sequencing technology and time-series algorithms, many studies have conducted systematic and transcriptional dynamics analyses to understand the timedependent progressive development of physiological processes and time-dependent gene expression in biological processes, such as those involved in transcriptional variation in skin wound healing (Theocharidis et al, 2020), changes in transcription profiles during healing after fractures (Coates et al, 2019), changes in transcriptional dynamics during oral and liver tumor progression (Jee et al, 2019;Kang et al, 2019), and changes in the transcriptome during organ and tissue development (Zhu et al, 2018). In this study based on next-generation sequencing, we used WGCNA co-expression module analysis, STEM and maSigPro time-related algorithms, and PPI network analysis to clarify the characteristics of multi-level biological processes and transcriptional dynamics after SMI.…”

Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer

“…Chitinase 3-like protein 2 (CHI3L2), a glycosyl hydrolase family member, encodes a protein similar to bacterial chitinase but lacking chitinase activity. Upregulation of CHI3L2 could increase the phosphorylation level of ERK1 and ERK2, thus inhibiting tumor cell mitosis and proliferation in glial cell tumors [ 33 , 34 ]. FYN Binding Protein 1 (FYB1) also is known as adhesion and degranulation-promoting adapter protein (ADAP).…”

The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts

“…Chronic infection and the interaction of cell surface molecules on these bacteria with the inflammatory and immune systems are important carcinogenesis mechanisms of F. nucleatum ( Gholizadeh et al, 2017 ). F. nucleatum was reported to trigger oncogene expression in the process of gingiva-derived mesenchymal stem cell differentiation ( Kang et al, 2020 ). CYP1B1 is an enzyme associated with angiogenesis that was found to be overexpressed in a wide variety of tumors ( D’Uva et al, 2018 ).…”