PCAT-1 facilitates breast cancer progression via binding to RACK1 and enhancing oxygen-independent stability of HIF-1a

Hypoxia induces a series of cellular adaptive responses that enable promotion of inflammation and cancer development. Hypoxia-inducible factor-1a (HIF-1a) is involved in the hypoxia response and cancer promotion, and it accumulates in hypoxia and is degraded under normoxic conditions. Here we identify prostate cancer associated transcript-1 (PCAT-1) as a hypoxiainducible long non-coding RNA (lncRNA) that regulates HIF1a 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-1a, thus protecting HIF-1a from RACK1-induced oxygen-independent degradation. These findings provide new insight into lncRNA-mediated mechanisms for HIF-1a stability and suggest a novel role of PCAT-1 as a potential therapeutic target for breast cancer.

Automated summary

PCAT-1, a hypoxia-inducible lncRNA, regulates HIF-1a stability to promote breast cancer progression, suggesting its potential as a therapeutic target.