Porphyromonas gingivalis Infection Promoted the Proliferation of Oral Squamous Cell Carcinoma Cells through the miR-21/PDCD4/AP-1 Negative Signaling Pathway.
Recent epidemiological studies have revealed that Porphyromonas gingivalis, a major pathogen in periodontal disease, is associated with the development of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gingivalis in OSCC proliferation and the relevant molecular mechanisms. A cellular proliferation model of OSCC Tca8113 cells infected by P. gingivalis at a multiplicity of infection (MOI) of 50 was established. Cell proliferation was drastically increased in the infected cells compared with the control cells, while the proportion of cells in S phase was increased and the proportion of cells in G1 phase was decreased in the infected cells compared with the control cells. Additionally, the levels of activator protein 1 (AP-1; c-Jun and c-Fos) and its target gene cyclin D1 were increased in P. gingivalis-infected Tca8113 cells compared with control cells. miR-21 expression was elevated when programmed cell death 4 (PDCD4) expression was downregulated. Cyclin D1 expression was regulated by miR-21, PDCD4, and AP-1. The disruption of the pathway by silencing c-Jun, blocking miR-21 expression, or overexpressing PDCD4 led to decreased cyclin D1 expression and inhibited cell proliferation. P. gingivalis DNA levels were positively correlated with miR-21 and c-Jun expression and negatively correlated with PDCD4 expression in clinical OSCC samples. Our findings indicated that P. gingivalis might promote OSCC proliferation by regulating cyclin D1 expression via the miR-21/PDCD4/AP-1 negative feedback signaling pathway.
['Chang|Chunrong|C|0000-0002-2940-3415', 'Wang|Hongyan|H|', 'Liu|Junchao|J|', 'Pan|Chunling|C|', 'Zhang|Dongmei|D|', 'Li|Xin|X|', 'Pan|Yaping|Y|']
D000818:Animals D051017:Apoptosis Regulatory Proteins D016866:Bacteroidaceae Infections D002294:Carcinoma, Squamous Cell D045744:Cell Line, Tumor D049109:Cell Proliferation D019938:Cyclin D1 D015536:Down-Regulation D005786:Gene Expression Regulation D006801:Humans D051379:Mice D035683:MicroRNAs D009055:Mouth D016966:Porphyromonas gingivalis D016755:Proto-Oncogene Proteins c-jun D016601:RNA-Binding Proteins D015398:Signal Transduction D018808:Transcription Factor AP-1
miR-21 AP-1 OSCC cell proliferation cyclin D1