The Positive Feedback of lncRNA ANRIL/miRNA-339-5p/ZBTB7A Suppresses Metastasis of Nasopharyngeal Carcinoma Cells via SREBP1-FASN

Disruptions in lipid metabolism can hasten disease progression and impose a heavier burden on patients with nasopharyngeal carcinoma (NPC). We previously observed a positive correlation between zinc finger and BTB domain-containing protein 7A (ZBTB7A) and the long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL), indicating a potential link between NPC and lipid metabolism; however, the underlying mechanism remains unclear. This study investigated primary NPC tissues that had significantly lower ZBTB7A expression than that in normal nasopharyngeal epithelium. Subsequent results confirmed that ANRIL promoted ZBTB7A expression by sponging miR-339-5p. ZBTB7A directly promoted ANRIL expression but inhibited SREBP1 and FASN expression. Thus, the ANRIL/miR-339-5p/ZBTB7A axis creates a positive feedback loop that suppresses the lipid pathway. Combining stable ANRIL overexpression with ZBTB7A shRNA effectively reduced lipid metabolism and the migratory, invasive, and metastatic capacities of NPC cells in vitro and in vivo. Furthermore, the SREBP inhibitor, fatostatin, enhanced the suppression of NPC metastasis. Our results indicated that interventions targeting ANRIL-shZBTB7A and SREBP inhibitors can effectively disrupt lipid metabolism and impair the invasive and metastatic properties of NPC cells. These findings provide valuable insights into the potential experimental strategies for inhibiting NPC metastasis.