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Comment
. 2022 May;12(5):e889.
doi: 10.1002/ctm2.889.

N6 -methyladenosine-RNA methylation promotes expression of solute carrier family 7 member 11, an uptake transporter of cystine for lipid reactive oxygen species scavenger glutathione synthesis, leading to hepatoblastoma ferroptosis resistance

Ronald A Hill  1 , Yong-Yu Liu  1
Affiliations
Comment

N6 -methyladenosine-RNA methylation promotes expression of solute carrier family 7 member 11, an uptake transporter of cystine for lipid reactive oxygen species scavenger glutathione synthesis, leading to hepatoblastoma ferroptosis resistance

Ronald A Hill et al. Clin Transl Med. 2022 May.
No abstract available

Keywords: METTL3; RNA methylation; SLC7A11 transporter; cystine; ferroptosis; hepatoblastoma.

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Figures

FIGURE 1
FIGURE 1
N 6‐methyladenosine (m6A) methylation upregulates expression of solute carrier family 7 member 11 (SLC7A11) and results in ferroptosis resistance. Chemotherapeutic agents can enhance m6A‐RNA methylation and cause metabolic stress with generation of reactive oxygen species (ROS) as well as phospholipid hydroperoxides (PLOOH) (lipid ROS) in cancer cells. Increased levels of lipid ROS can trigger (→) iron‐dependent ferroptosis to kill cancer cells; however, reduced glutathione (GSH) synthesized from intracellular cystine can constrain (┬) lipid ROS and avert ferroptotic death. Enhanced N 6‐methyladenosine (m6A) RNA methylation catalyzed by methyltransferase‐like 3 (METTL3) enhances the stability of SLC7A11 mRNA, thus upregulating its translation to protein, in turn increasing uptake of cystine for GSH synthesis
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