LOXL1-AS1 suppresses ferroptosis in cervical cancer through m6A-dependent regulation of TFRC.

Transferrin receptor (TFRC) is essential for iron uptake and may regulate ferroptosis, a form of iron-dependent cell death implicated in cervical cancer (CC). Bioinformatic analyses (GEPIA, UALCAN, SRAMP, starBase) were combined with in vitro and in vivo experiments. CC cell lines were transfected with shRNAs or overexpression plasmids targeting TFRC and LOXL1-AS1. Proliferation was assessed by colony formation, EdU staining, and Ki-67 immunostaining. Ferroptosis was evaluated by measuring malondialdehyde (MDA), lipid ROS, Fe⁺, and ferroptosis-related proteins. RNA pull-down, RIP, and MeRIP assays were used to explore m6A-dependent regulation, and actinomycin D assays assessed mRNA stability. TFRC and LOXL1-AS1 were upregulated in CC and associated with poor prognosis. TFRC promoted CC cell proliferation and inhibited ferroptosis. LOXL1-AS1 positively regulated TFRC by stabilizing its mRNA via an m6A-IGF2BP2-dependent mechanism. Rescue experiments confirmed that TFRC overexpression reversed the effects of LOXL1-AS1 knockdown. In vivo, LOXL1-AS1 depletion suppressed tumor growth and enhanced ferroptosis. LOXL1-AS1 promoted CC progression by stabilizing TFRC mRNA through m6A-IGF2BP2 interaction, suppressing ferroptosis. Targeting the LOXL1-AS1/IGF2BP2/TFRC axis may offer a potential therapeutic strategy for CC.