N 6 -methyladenosine modified GNAI2 accelerates the tumorigenesis of gastric cancer by inhibiting ferroptosis

Emerging evidence had indicated that ferroptosis and m ⁶ A modification play important roles in mRNA transcription. However, the role of m ⁶ A modified GNAI2 on the gastric cancer (GC) ferroptosis and tumorigenesis is still unclear. In this study, the elevated GNAI2 expression indicated a poor prognosis of GC specimens and GNAI2 accelerated the GC tumorigenesis in vitro . Functionally, transmission electron microscopy, iron ion (Fe ²⁺ ) concentration, fluorescent probe FerroOrange and lipid peroxidation analysis revealed that GNAI2 could repress the ferroptosis of GC. Mechanistically, GNAI2 was modified by m ⁶ A reader hnRNPA2B1, and hnRNPA2B1 enhanced the stability of GNAI2 mRNA by m ⁶ A manner. In vivo , GNAI2 silencing repressed the GC tumor growth and accelerated the Fe ²⁺ concentration in tumor tissue. Overall, these data concluded that m ⁶ A modified GNAI2 accelerated the tumorigenesis of gastric cancer by inhibiting ferroptosis, which provides a novel insight for GC treatment.