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

• Main Authors: Jianlong Wang (Author), Xuyi Chen (Author), Haijuan Hu (Author), Mengting Yao (Author), Yanbiao Song (Author), Aimin Yang (Author), Xiuhua Xu (Author), Ning Zhang (Author), Jianzhao Gao (Author), Bin Liu (Author)
• Format: Book
• Published: Elsevier, 2021-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2162-2531; 10.1016/j.omtn.2021.02.034
• Keywords: breast cancer; HIF-1α; hypoxia; PCAT-1; RACK1; Therapeutics. Pharmacology; RM1-950
• Source: Molecular Therapy: Nucleic Acids, Vol 24, Iss , Pp 310-324 (2021)

Hypoxia induces a series of cellular adaptive responses that enable promotion of 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 is degraded under normoxic conditions. Here we identify prostate cancer associated transcript-1 (PCAT-1) as a hypoxia-inducible long non-coding RNA (lncRNA) that regulates 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 new insight into lncRNA-mediated mechanisms for HIF-1α stability and suggest a novel role of PCAT-1 as a potential therapeutic target for breast cancer.