RNA sequencing reveals a key role for the long non-coding RNA MIAT in regulating neuroblastoma and glioblastoma cell fate

Abstract

Myocardial Infarction Associated Transcript (MIAT) is a subnuclear lncRNA that interferes with alternative splicing and is associated with increased risk of various heart conditions and nervous system tumours. The current study aims to elucidate the role of MIAT in cell survival, apoptosis and migration in neuroblastoma and glioblastoma multiforme. To this end, MIAT was silenced by MIAT-specific siRNAs in neuroblastoma and glioblastoma cell lines, and RNA sequencing together with a series of functional assays were performed. The RNA sequencing has revealed that the expression of an outstanding number of genes is altered, including genes involved in cancer-related processes, such as cell growth and survival, apoptosis, reactive oxygen species (ROS) production and migration. Furthermore, the functional studies have confirmed the RNA sequencing leads, with our key findings suggesting that MIAT knockdown eliminates long-term survival and migration and increases basal apoptosis in neuroblastoma and glioblastoma cell lines. Taken together with the recent demonstration of the involvement of MIAT in glioblastoma, our observations suggest that MIAT could possess tumour-promoting properties, thereby acting as an oncogene, and has the potential to be used as a reliable biomarker for neuroblastoma and glioblastoma and be employed for prognostic, predictive and, potentially, therapeutic purposes for these cancers.

Keywords: Apoptosis; Glioblastoma; MIAT; Neuroblastoma; Oxidative stress; RNA sequencing.