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分析感染具核梭杆菌的口腔上皮细胞中的差异表达基因,以揭示与口腔癌相关的基因。

Analysis of differentially expressed genes in oral epithelial cells infected with Fusobacterium nucleatum for revealing genes associated with oral cancer.

机构信息

Department of Periodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.

Department of Oral Biology, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.

出版信息

J Cell Mol Med. 2021 Jan;25(2):892-904. doi: 10.1111/jcmm.16142. Epub 2020 Dec 2.

Abstract

Accumulating evidence links Fusobacterium nucleatum with tumorigenesis. Our previous study demonstrated that F. nucleatum infection can induce epithelial-mesenchymal transition (EMT) in oral epithelial cells and elaborated a probable signal pathway involved in the induction of EMT. However, the comprehensive profiling and pathways of other candidate genes involved in F. nucleatum promoting malignant transformation remain largely elusive. Here, we analysed the transcriptome profile of HIOECs exposed to F. nucleatum infection. Totally, 3307 mRNAs (ǀLog2FCǀ >1.5) and 522 lncRNAs (ǀLog2FCǀ >1) were identified to be differentially expressed in F. nucleatum-infected HIOECs compared with non-infected HIOECs. GO and KEGG pathway analyses were performed to investigate the potential functions of the dysregulated genes. Tumour-associated genes were integrated, and top 10 hub genes (FYN, RAF1, ATM, FOS, CREB, NCOA3, VEGFA, JAK2, CREM and ATF3) were identified by protein-protein interaction (PPI) network, and Oncomine was used to validate hub genes' expression. LncRNA-hub genes co-expression network comprising 67 dysregulated lncRNAs were generated. Together, our study revealed the alteration of lncRNA and potential hub genes in oral epithelial cells in response to F. nucleatum infection, which may provide new insights into the shift of normal to malignant transformation initiated by oral bacterial infection.

摘要

越来越多的证据表明具核梭杆菌与肿瘤发生有关。我们之前的研究表明,具核梭杆菌感染可诱导口腔上皮细胞发生上皮-间充质转化(EMT),并阐述了一个可能涉及 EMT 诱导的信号通路。然而,具核梭杆菌促进恶性转化的其他候选基因的综合分析和途径在很大程度上仍未被揭示。在这里,我们分析了暴露于具核梭杆菌感染的 HIOECs 的转录组谱。与未感染的 HIOECs 相比,在具核梭杆菌感染的 HIOECs 中总共鉴定出 3307 个 mRNA(|Log2FC|>1.5)和 522 个 lncRNA(|Log2FC|>1)差异表达。GO 和 KEGG 通路分析被用来研究失调基因的潜在功能。肿瘤相关基因被整合,通过蛋白质-蛋白质相互作用(PPI)网络鉴定出前 10 个枢纽基因(FYN、RAF1、ATM、FOS、CREB、NCOA3、VEGFA、JAK2、CREM 和 ATF3),并使用 Oncomine 验证了枢纽基因的表达。生成了包含 67 个失调 lncRNA 的 lncRNA-枢纽基因共表达网络。总之,我们的研究揭示了口腔上皮细胞对具核梭杆菌感染的 lncRNA 和潜在枢纽基因的改变,这可能为口腔细菌感染引发的正常向恶性转化的转变提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe7/7812288/7a4b118bff87/JCMM-25-892-g001.jpg

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