METTL3 regulates PM_2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells

N⁶-methyladenosine (m⁶A) is implicated in alteration of cellular biological processes caused by exogenous environmental factors. However, little is known about the role of m⁶A in airborne fine particulate matter (PM_2.5)-induced adverse effects. Thus, we investigated the role of m⁶A modification in PM_2.5-induced airway epithelial cell injury. We observed a methyltransferase-like 3 (METTL3)-dependent induction of m⁶A modification after PM_2.5 treatment in HBE and A549 cells. METTL3 knockdown attenuated PM_2.5-induced apoptosis and arrest of cell cycle. mRNA sequencing and RNA N⁶-methyladenosine binding protein immunoprecipitation (Me-RIP) assay identified m⁶A-modified oxidative stress induced growth inhibitor 1 (OSGIN1) as the target gene of METTL3. Knockdown of METTL3 resulted a shorter mRNA half-life of OSGIN1 by catalyzing its m⁶A modification. Knockdown of METTL3 or OSGIN1 attenuated cell apoptosis, arrest of cell cycle and autophagy induced by PM_2.5. In conclusion, METTL3 may mediate PM_2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells. Our work uncovered a critical role of METTL3 in PM_2.5-induced airway epithelial cell injury and provided insight into the vital role of m⁶A modification in PM_2.5-induced human hazards.