Therapeutic targeting of the SLC39A13-AS1/TCF20/RUNX1 axis inhibits glutamine metabolism and ovarian cancer progression

“Glutamine addiction” is among the key features of tumor metabolic reprogramming and is an important target for tumor therapy. Unfortunately, the mechanisms underlying the abnormal expression of genes related to glutamine metabolism in ovarian cancer (OC) remain unclear. Here, we conducted in vitro and in vivo experiments, integrated data from multiple bioinformatics databases and demonstrated that the SLC39A13-AS1/TCF20/RUNX1 axis represents a key molecular mechanism promoting glutamine metabolism and the malignant progression of OC. Mechanistically, SLC39A13-AS1 increases glutamine metabolism and the malignant progression of OC by activating the RUNX1 pathway through its interaction with TCF20. Notably, the synthetic inhibitory peptide WTP-19 decreases the expression of RUNX1 pathway-related genes by blocking the interaction between SLC39A13-AS1 and TCF20, which ultimately inhibits glutamine metabolism in and the malignant progression of OC cells. Furthermore, the prognostic model constructed on the basis of genes related to the SLC39A13-AS1/TCF20/RUNX1 axis has potential prognostic value for OC patients. Collectively, our findings identify SLC39A13-AS1 as a previously unrecognized regulator of glutamine metabolism in ovarian cancer, provide new insights into lncRNA-mediated metabolic reprogramming, and suggest that targeting this regulatory pathway may represent a potential therapeutic approach for OC.