Regulatory Role of the Clock Gene Nr1d1 in Oxygenated Polycyclic Aromatic Hydrocarbons 9-Fluorenone Induced Tumorigenesis

• • 9-Fluorenone exposure at 10 and 30 μmol·L−1 significantly increased HepG2 cell proliferation (colony formation and EdU staining), indicating a dose-dependent tumor-promoting effect. • • Nr1d1 mRNA expression was suppressed by 9-fluorenone in a dose-dependent manner, with a notable reduction in oscillation amplitude in synchronized cells, implicating circadian disruption. • • Pretreatment with the Nr1d1 agonist SR9009 effectively blocked 9-fluorenone-induced proliferation, confirming Nr1d1 as a key mediator and potential therapeutic target. • • The study establishes a mechanistic link between environmental OPAH exposure and clock gene dysregulation, highlighting Nr1d1 as a biomarker for OPAH-induced carcinogenesis.