MIAT Is an Upstream Regulator of NMYC and the Disruption of the MIAT/NMYC Axis Induces Cell Death in Amplified Neuroblastoma Cell Lines.

Neuroblastoma (NBL) is the most common extracranial childhood malignant tumor and represents a major cause of cancer-related deaths in infants. amplification or overexpression is associated with the malignant behavior of NBL tumors. In the present study, we revealed an association between long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) and amplification in NBL cell lines and MIAT expression in NBL tissue samples. MIAT silencing induces cell death only in cells with amplification, but in NBL cells without amplification it decreases only the proliferation. MIAT downregulation markedly reduces the NMYC expression in -amplified NBL cell lines and c-Myc expression in non-amplified NBL cell lines, but the ectopic overexpression or downregulation of NMYC did not affect the expression of MIAT. Moreover, MIAT downregulation results in decreased ornithine decarboxylase 1 (ODC1), a known transcriptional target of oncogenes, and decreases the glycolytic metabolism and respiratory function. These results indicate that MIAT is an upstream regulator of NMYC and that MIAT/NMYC axis disruption induces cell death in -amplified NBL cell lines. These findings reveal a novel mechanism for the regulation of NMYC in NBL, suggesting that MIAT might be a potential therapeutic target, especially for those with amplification.