Targeting AKT induced Ferroptosis through FTO/YTHDF2-dependent GPX4 m6A methylation up-regulating and degradating in colorectal cancer.

ABSTRACT: Ferroptosis is a new type of iron-dependent programmed cell death induced by lipid peroxidation. However, the underlying mechanisms and function in tumor therapy still remain undisclosed especially in post-transcription regulation. Here, we found that targeting AKT significantly induced GPX4 dependent ferroptosis and suppressed colorectal cancer growth both in vitro and in vivo. During this process, demethylase FTO was downregulated, which increased the m6A methylation level of GPX4, subsequently recognized by YTHDF2 and degraded. Prediction results showed that there are three potential methylated sites (193/647/766), and 193 site was identified as the right one, which was demethylated by FTO and read by YTHDF2. In parallel, AKT inhibition caused the accumulation of ROS which had a negativ

SUBMITTER: Zhang G 

PROVIDER: S-EPMC10724184 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature