Kang Wenyan, Sun Tianyong, Tang Di, Zhou Jiannan, Feng Qiang
Department of Human Microbiome, School and Hospital of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.
Department of Periodontology, School of Stomatology, Shandong University, Jinan, China.
Front Cell Dev Biol. 2020 Jan 14;7:359. doi: 10.3389/fcell.2019.00359. eCollection 2019.
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 , 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 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 -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 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 may trigger the expression of cancer-related genes in normal gingiva-derived stem cells.
对口腔鳞状细胞癌和结肠癌具有致病作用，而持续暴露于 所诱导的正常人类细胞中基因表达持续改变的影响仍不清楚。在本研究中，使用微阵列显著谱（maSigPro）分析来获取经 刺激3天、7天、14天和21天的牙龈来源间充质干细胞（GMSCs）的转录组谱，结果显示790个（九个簇）差异表达基因（DEGs），这些基因在细胞黏附连接和癌症相关途径中显著富集。基于短时间序列表达挖掘器（STEM）分析，根据动态基因表达模式将GMSCs中的所有表达基因分为50个簇，并且在经 处理的GMSCs中三个基因簇的表达水平与预测值显著不同。在790个DEGs中，在 刺激期间鉴定出50个肿瘤相关基因（TAGs；如L3MBTL4、CD163、CCCND2、CADM1、BCL7A和IGF1）和五个核心动态DEGs（PLCG2、CHI3L2、L3MBTL4、SH2D2A和NLRP3）。基因共表达网络数据库（GeneMANIA）分析结果表明，PLCG2、CHI3L2、SH2D2A和NLRP3以及其他20种蛋白质形成了一个复杂网络，其中12个基因在癌症相关途径中富集。基于五个核心动态DEGs，从公共资源中获得相关的 microRNA（miRNA）和转录因子（TF），并构建了由相关TF、miRNA和mRNA组成的综合网络。结果表明，这些基因受几种miRNA（如miR - 372 - 3p、miR - 603和miR - 495 - 3p）和几种TF（包括CREB3、GATA2和SOX4）的调控。我们的研究表明，长期受 刺激可能会触发正常牙龈来源干细胞中癌症相关基因的表达。
