LncRNA SLC7A11AR promotes lung adenocarcinoma progression by inhibiting ferroptosis via promoting SLC7A11 expression.

Non-small cell lung cancer (NSCLC) is a prevalent classification of human lung cancer with a variety of clinical pathological features. Several key factors and associated signaling pathways have played pivotal roles in the progression of NSCLC and serve as potential therapeutic targets. However, the therapeutic efficacy is still limited, and novel biomarkers and key regulators are inevitable. We found a human-specific long non-coding RNA (lncRNA, ENST00000504300) induced by the inflammatory pathway, termed SLC7A11AR (SLC7A11 associated lncRNA), which was highly expressed in lung adenocarcinoma (LUAD) cell lines but not in lung squamous cell carcinoma (LUSC). Our research showed that higher SLC7A11AR expression correlates with a poorer clinical prognosis. Depleting SLC7A11AR restrains tumor cell proliferation, migration, and xenograft tumor formation by promoting ferroptosis. Bioinformatic analysis and dual luciferase reporter assays revealed that SLC7A11AR binds directly to miR-150-5p, weakening the inhibition on its downstream target SLC7A11, a key ferroptosis inhibitor in NSCLC. In cancerous tissues, SLC7A11AR was upregulated, while miR-150-5p was downregulated compared to control tissues. Enforced miR-150-5p expression inhibited tumor growth. Moreover, ASOs against SLC7A11AR alone or with a ferroptosis agonist significantly suppressed tumor progression. Our results suggest that the SLC7A11AR/miR-150-5p/SLC7A11 axis plays an oncogenic role in LUAD development and has the potential to be novel therapeutic targets, presenting new opportunities for LUAD treatment in the future.