Osteosarcoma (OS) is the most common histological form of primary bone cancer. Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) functions as an oncogene in some cancers. However, the functional role of NEAT1 in OS metastasis remains elusive. In the present study, we found that NEAT1 expression was significantly increased in OS tissues and cell lines. Overexpression of NEAT1 in OS tissues was correlated with higher clinical stage, distant metastasis and poorer prognosis. Loss- and gain-of-function assays showed that NEAT1 positively regulated metastasis in vitro and in vivo. In addition, ectopic expression of NEAT1 also induced epithelial-mesenchymal transition (EMT). Mechanistic studies revealed that NEAT1 epigenetically suppresses E-cadherin expression through association with G9a-DNMT1-Snail complex. Taken together, our study reveals a critical epigenetic mechanism underlying NEAT1-mediated metastasis.
Keywords: DNA methylation; DNMT1; G9a; H3K9me2; NEAT1; Snail.