Long non-coding RNA KRT19P3 suppresses proliferation and metastasis through COPS7A-mediated NF-κB pathway in gastric cancer.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in gastric cancer (GC). LncRNA expression microarray data indicate that KRT19P3 (Keratin 19 Pseudogene 3) is downregulated in GC samples. However, the expression pattern and molecular mechanism of KRT19P3 in GC have not been characterized. The present study confirmed the downregulation of KRT19P3 in GC tissues and cells. Decreased expression of KRT19P3 was correlated with larger tumor size, advanced TNM stage, Lauren's classification, positive lymph node metastasis, and poor prognosis. Enforced expression of KRT19P3 significantly inhibited cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, KRT19P3 knockdown had opposite effects. Mechanistically, RNA pull-down and RNA immunoprecipitation assay revealed that KRT19P3 could directly bind COPS7A. KRT19P3 enhanced COPS7A protein stability in GC cells, and KRT19P3 suppressed GC cell proliferation and metastasis partly through regulation of COPS7A expression. COPS7A could promote deubiquitinylation of IκBα, which was executed by CSN-associated deubiquitinylase USP15, and then KRT19P3 inactivated nuclear factor kappa-B (NF-κB) signaling pathway in a COPS7A-dependent manner. For the first time, we revealed that KRT19P3 could suppress tumor growth and metastasis through COPS7A-mediated NF-κB pathway, which may serve as potential targets for treatment of GC in the future.