PCAT-1 facilitates breast cancer progression via binding to RACK1 and enhancing oxygen-independent stability of hypoxia-inducible factor-1α

Abstract Hypoxia induces a series of cellular adaptive responses that enable to promote inflammation and cancer development. Hypoxia-inducible factor-1α (HIF-1α) is involved in the hypoxia response and cancer promotion, and it accumulates in hypoxia and degraded under normoxic conditions. Here we identify prostate cancer associated transcript-1 (PCAT-1) as a hypoxia-inducible lncRNA that regulates the HIF-1α stability, crucial for cancer progression. Extensive analyses of clinical data indicate that PCAT-1 is elevated in breast cancer patients and is associated with pathological grade, tumor size and poor clinical outcomes. Through gain and loss of function experiments, we find that PCAT-1 promotes hypoxia-associated breast cancer progression including growth, migration, invasion, colony formation, and metabolic regulation. Mechanistically, PCAT-1 directly interacts with the receptor of activated protein C kinase-1 (RACK1) protein and prevents RACK1 from binding to HIF-1α, thus protecting HIF-1α from RACK1-induced oxygen-independent degradation. These findings provide a new insight into lncRNA-mediated mechanisms for HIF-1α stability and suggest that a novel role of PCAT-1 as a potential therapeutic target for breast cancer.