METTL3-mediated m6A modification of SLC7A11 enhances nasopharyngeal carcinoma radioresistance by inhibiting ferroptosis
Zili Dai, Baisheng Lin, Maohua Qin, Yunen Lin, Li Wang, Kai Liao, Guofeng Xie, Feixiang Wang, Jian Zhang
Abstract
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC); nonetheless, radioresistance remains the leading cause of localized recurrence. Our study demonstrates a significant increase in the N6-methyladenosine (m6A) methylase METTL3 in NPC and other tumors. Mechanistically, METTL3 acts as an m6A methylase, enhancing the m6A modification of the solute carrier family 7 member 11 (SLC7A11) transcript, which increases its stability and expression, thereby inhibiting radiation-induced ferroptosis and ultimately inducing radioresistance in NPC. Furthermore, silencing SLC7A11 or employing the ferroptosis inducer Erastin negated the promoting effect of METTL3 on NPC cell radioresistance. These findings suggest that METTL3 could be a novel therapeutic target for overcoming radiotherapy resistance in NPC.