PITRM1-AS1 attenuates the ferroptosis of gastric cancer via TAF1-mediated KDM3B transcription

This study aimed to identify ferroptosis-related lncRNAs in gastric cancer (GC), with a view to providing novel insights into GC therapy by inducing ferroptosis. Bioinformatics analysis was conducted to screen ferroptosis-related lncRNAs and further identified their expression at the tissue and cellular levels. The malignant phenotypes and ferroptosis characteristics of GC cells were measured by CCK-8, colony formation, transwell assays as well as iron, Fe 2+ , MDA detection. The molecular mechanism mediated by PITRM1-AS1 was probed through co-expression analysis, RNA immunoprecipitation, dual-luciferase reporter, and rescue experiments. Besides, the nude mouse model was applied to verify the ferroptosis effect caused by PITRM1-AS1 in vivo. PITRM1-AS1 was identified as a ferroptosis-related lncRNA highly expressed in GC. Knockdown of PITRM1-AS1 significantly weakened the proliferation and metastatic abilities of GC cells while promoting ferroptosis. Co-expression results presented that KDM3B was a downstream target gene positively regulated by PITRM1-AS1. Moreover, mechanism studies demonstrated that PITRM1-AS1 directly bind to transcription factor TAF1 and promoted TAF1-mediated transcription of KDM3B. Furthermore, rescue studies confirmed that KDM3B overexpression partially abrogated the ferroptosis effect and tumor suppression induced by PITRM1-AS1 silencing. In summary, these results revealed the function of PITRM1-AS1 in GC and disclosed a novel PITRM1-AS1-mediated TAF1/KDM3B/SLC7A11 regulatory axis. Our findings offer novel insights into the molecular mechanisms underlying ferroptosis-related GC.