Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma

作者：Zhenming Li, You Fu, Yuhua Hu, Yun Zhu, Longwei Hu, Chaoji Shi, Yi Zhang, Jianjun Zhang, Shanghui Zhou · 发表于：BMC Oral Health · 年份：2023 · DOI：10.1186/s12903-023-02887-2 · 被引用次数：13 · 研究领域：Oral Health Pathology and Treatment、Head and Neck Cancer Studies、Oral and Maxillofacial Pathology

BACKGROUND: Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. METHODS: Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. RESULTS: In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were fou...