A METTL3-NFE2L3 axis mediates tumor stemness and progression in lung adenocarcinoma.

ABSTRACT: The progression of lung adenocarcinoma is primarily driven by cancer stem cells (CSCs), which have self-renewal capabilities and confer resistance to therapies, including neoadjuvant treatments combining chemotherapy and immune checkpoint inhibitors. In this study, we identified that OV6⁺ tumor cells exhibit stem-like characteristics and are notably enriched in patients with non-major pathological response, closely associated with resistance to combination therapies. Hypoxia and HIF1α were found to drive the formation of OV6⁺ CSCs. METTL3, a methyltransferase, was revealed as a critical regulator of OV6⁺ CSCs by stabilizing NFE2L3 messenger RNA via an N⁶-methyladenosine-dependent manner, thereby up-regulating NFE2L3 and activating the intr

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12007586 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature