The lncRNA MIAT is regulated by NFYA to promote glioblastoma multiforme through the miR-221-3p/SIRT1 axis

Glioblastoma multiforme (GBM) is an aggressive form of brain tumor that accounts for 47.7 % of all brain and central nervous system (CNS) tumor types with poor five-year survival. In addition to genetic mutations and altered protein expressions, the aberrant expression of long non-coding RNAs also regulates GBM progression. Myocardial infarction-associated transcript (MIAT) is a well-known long non-coding RNA (lncRNA) that has been implicated in the development of various cancers, but its functional role in GBM is still unclear. The Cancer Genome Atlas (TCGA)-GBM data have shown significantly high levels of MIAT expression in brain and CNS tumors such as gliomas, glioblastomas, pheochromocytomas, and paragangliomas. The functional role of MIAT was assessed in GBM cell line models—LN18, LN229, and U87MG—by the knockdown of its expression. An increased migration, invasion, and survival were observed in cells expressing MIAT compared with those in knockdown cells. In addition, the transcription factor NFYA was found to bind to the promoter resulting in MIAT overexpression. The knock-down of NFYA and subsequent loss of MIAT expression confirmed the NFYA-mediated transcription regulation of MIAT. Furthermore, the knockdown of MIAT led to an upregulation of miR-221-3p and a downregulation of its target gene SIRT1. Overall, the study illustrated that MIAT promoted GBM progression through increased cell migration, invasion, and survival. Transcriptional activation by NFYA and the MIAT/miR-221-3p/SIRT1 axis revealed a novel regulatory role of MIAT in GBM. Schematic illustration of NFYA-mediated lncRNA-MIAT upregulation in GBM progression. [Display omitted] •TCGA-GBM data showed high levels of MIAT expression in Glioblastoma multiforme (GBM).•MIAT was found to be upregulated in GBM cells by the effective binding of transcription factor NFYA to its promoter.•MIAT knockdown caused the upregulation of miR-221-3p in GBM cells indicating their interaction.•MiR-221-3p upregulation decreases SIRT1, which is significantly involved in GBM signaling pathways.•The study reveals a novel regulatory role of MIAT in GBM through the MIAT/miR-221-3p/SIRT1 axis.