LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

Abstract

PELATON is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 ( LINC01272 ). The known reports showed that PELATON functions as an onco-lncRNA or a suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found that PELATON , as an onco-lncRNA, alleviates the ferroptosis driven by mutant p53 and promotes mutant p53 -mediated GBM proliferation. We also first confirmed that PELATON is a new ferroptosis suppressor lncRNA that functions as a ferroptosis inhibitor mainly by mutant P53 mediating the ROS ferroptosis pathway, which inhibits the production of ROS, reduces the levels of divalent iron ions, promotes the expression of SLC7A11 , and inhibits the expression of ACSL4 and COX2 . PELATON can inhibit the expression of p53 in p53 wild-type GBM cells and regulate the expression of BACH1 and CD44 , but it has no effect on p53 , BACH1 and CD44 in p53 mutant GBM cells. PELATON and p53 can form a complex through the RNA binding protein EIF4A3. Knockdown of PELATON resulted in smaller mitochondria, increased mitochondrial membrane density, and enhanced sensitivity to ferroptosis inducers to inhibit GBM cell proliferation and invasion. In addition, we established a favourite prognostic model with NCOA4 and PELATON . PELATON is a promising target for the prognosis and treatment of GBM.