AUTHOR=Fu Haijuan , Zhang Zhaoyu , Li Danyang , Lv Qingqing , Chen Simin , Zhang Zuping , Wu Minghua 

TITLE=LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.817737

DOI=10.3389/fonc.2022.817737

ISSN=2234-943X

ABSTRACT=<p><italic>PELATON</italic> is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 (<italic>LINC01272</italic>). The known reports showed that <italic>PELATON</italic> 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 <italic>PELATON</italic>, as an onco-lncRNA, alleviates the ferroptosis driven by mutant <italic>p53</italic> and promotes mutant <italic>p53</italic>-mediated GBM proliferation. We also first confirmed that <italic>PELATON</italic> is a new ferroptosis suppressor lncRNA that functions as a ferroptosis inhibitor mainly by mutant <italic>P53</italic> mediating the ROS ferroptosis pathway, which inhibits the production of ROS, reduces the levels of divalent iron ions, promotes the expression of <italic>SLC7A11</italic>, and inhibits the expression of <italic>ACSL4</italic> and <italic>COX2</italic>.<italic>PELATON</italic> can inhibit the expression of <italic>p53</italic> in <italic>p53</italic> wild-type GBM cells and regulate the expression of <italic>BACH1</italic> and <italic>CD44</italic>, but it has no effect on <italic>p53</italic>, <italic>BACH1</italic> and <italic>CD44</italic> in <italic>p53</italic> mutant GBM cells. <italic>PELATON</italic> and <italic>p53</italic> can form a complex through the RNA binding protein EIF4A3. Knockdown of <italic>PELATON</italic> 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 <italic>NCOA4</italic> and <italic>PELATON</italic>. <italic>PELATON</italic> is a promising target for the prognosis and treatment of GBM.</p>