m6A-enriched SSTR5-AS1 regulates ferroptosis through recruiting FAM120A to stabilize UHRF1 mRNA in esophageal cancer

Long non-coding RNA SSTR5-AS1 is upregulated in esophageal cancer (EC) and correlates with poor prognosis. This study investigates its role in EC progression and its underlying mechanisms. In this study, SSTR5-AS1 is significantly overexpressed in EC tissues and cancer cell lines, correlating with poor prognosis. Functional assays reveal that SSTR5-AS1 enhances cell proliferation, colony formation, migration, and invasion. Knockdown of SSTR5-AS1 induces ferroptosis, evidenced by increased lipid ROS, Fe 2+ , and MDA levels, and decreased GSH levels. Ferroptosis inhibitors reverse these effects. SSTR5-AS1 stabilizes UHRF1 mRNA through interaction with FAM120A. Mechanistically, the stability of SSTR5-AS1 is maintained by IGF2BP1 and METTL3 in an m6A-dependent manner. In conclusion, SSTR5-AS1 promotes EC progression by inhibiting ferroptosis and stabilizing UHRF1 through the SSTR5-AS1 /FAM120A/UHRF1 axis. IGF2BP1 and METTL3 play crucial roles in regulating SSTR5-AS1 stability via m6A modification. These findings highlight SSTR5-AS1 as a potential therapeutic target and provide new insights into m6A-mediated regulation in cancer.