ZFAS1 Orchestrates Stress-Induced Autophagy in Ovarian Cancer via miR302 Suppression and BNIP3L Upregulation

Autophagy plays a multifaceted role in cancer, acting as a tumor suppressor in early stages while promoting survival in advanced disease. In ovarian cancer, the regulatory landscape of autophagy, particularly the role of long non-coding RNAs (lncRNAs), remains poorly defined. Here, we identify the lncRNA ZFAS1 as a key modulator of autophagy under starvation-induced conditions in high-grade serous ovarian cancer (HGSOC). Transcriptomic and functional analyses reveal consistent upregulation of ZFAS1 during autophagy induction. Silencing ZFAS1 disrupts autophagic flux, leading to the accumulation of p62 and LC3, indicative of impaired autophagy clearance. Mechanistically, ZFAS1 suppresses miR302, thereby enhancing BNIP3L expression, a known mitophagy regulator that promotes mitochondrial clearance and survival un-der metabolic stress. Clinical dataset analyses confirm a significant correlation be-tween ZFAS1 overexpression, BNIP3L upregulation, and poor survival outcomes in ovarian cancer patients. While autophagy exerts tumor-suppressive effects in some in-stances, our data reveals a context-specific lncRNA-mediated mechanism by which autophagy supports tumor survival. These findings define a novel ZFAS1-miR302-BNIP3L axis and highlight ZFAS1 as a potential target for disrupting autophagy-dependent resistance in ovarian cancer.