NEAT1 induces osteosarcoma development by modulating the miR-339-5p/TGF-β1 pathway.

Abstract

The long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been recognized as a tumor oncogene involved in the development of multiple cancers. However, the function of NEAT1 and its molecular mechanism in osteosarcoma (OS) remain unclear. First, we detected the NEAT1 expression in OS cell lines by performing quantitative reverse-transcription polymerase chain reaction. Next, the effects of NEAT1 on OS cell growth, apoptosis, migration, and invasion were tested by lentivirus-mediated downregulation. We observed that inhibition of NEAT1 restrained OS cell progression greatly. Interestingly, in the last few years, increasing studies have shown that some lncRNAs can act as miRNA sponges and reduce the amount of the same. Here, we found that NEAT1 can modulate OS development via sponging miR-339-5p. MiR-339-5p was significantly decreased in OS cells, and its overexpression can remarkably repress the OS proliferation. These results indicated that NEAT1 could function as a tumor oncogene in OS by inhibiting miR-339-5p in vitro. Then, the following assays validated that transforming growth factor β1 (TGF-β1) can act as a functional target of miR-339-5p in OS cells. Finally, we indicated that NEAT1 could mediate TGF-β1 expression by competitively sponging miR-339-5p. NEAT1 induced OS cell proliferation and cell mobility by binding to miR-339-5p and increasing TGF-β1 in OS. It was demonstrated in our study that lncRNA NEAT1 could impede miR-339-5p expression to maintain the expression of TGF-β1, which led to the development of OS. Our findings implied that the novel identified NEAT1/miR-339-5p/TGF-β1 axis might be a new molecular pathway or therapeutic target for OS diagnosis and treatment.