NEAT1 is Required for Survival of Breast Cancer Cells Through FUS and miR-548

Abstract

Increasing evidence shows that long noncoding RNAs (lncRNAs) have important roles in the regulation of multiple cellular processes, including cell division, cell growth, and apoptosis, as well as cancer metastasis and neurological disease progression; however, the mechanism of how lncRNAs regulate these processes is not well established. In this study, we demonstrated that downregulating the expression of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in breast cancer cells inhibited cell growth and induced cell apoptosis. In addition, the RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS) physically interacted with NEAT1, and reducing the expression of FUS/TLS also induced cell apoptosis. Multiple miRNAs were identified as regulators of NEAT1, but only overexpression of miR-548ar was able to decrease NEAT1 expression and promote apoptosis. These results indicate a novel interaction between NEAT1, miR-548ar-3p, and FUS and their role in the regulation of breast cancer cell apoptosis.