NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2

Abstract

Long noncoding RNA NBAT1 (neuroblastoma associated transcript 1) regulates cell proliferation and invasion by interacting with PRC2 (polycomb repressive complex 2) member EZH2 (enhancer of zeste 2). Decreased expression of NBAT1 is associated with poor clinical outcome in neuroblastomas. However, the roles of NBAT1 in other cancers remain unknown. Here, we report that NBAT1 is down-regulated in various types of cancer. Particularly, reduced NBAT1 in breast cancer is associated with tumor metastasis and poor patient prognosis. In vitro, ectopic NBAT1 inhibits migration and invasion of breast cancer cells. Mechanistic study shows that NBAT1 is associated with PRC2 member EZH2 and regulates global gene expression profile. Among them, DKK1 (dickkopf WNT signaling pathway inhibitor 1) is found to be regulated by NBAT1 in a PRC2 dependent manner, and is responsible for NBAT1’s effects in inhibiting migration and invasion of breast cancer cells. Taken together, our study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis.