biostudies-literatureZhang SNatural Science Foundation of Shandong ProvinceNational Natural Science Foundation of China699-717https://www.ebi.ac.uk/biostudies/studies/S-EPMC8905236biostudies-literatureUnknown27As one of the most common post-transcriptional modifications of mRNAs and noncoding RNAs, N⁶-methyladenosine (m⁶A) modification regulates almost every aspect of RNA metabolism. Evidence indicates that dysregulation of m⁶A modification and associated proteins contributes to glioblastoma (GBM) progression. However, the function of fat mass and obesity-associated protein (FTO), an m⁶A demethylase, has not been systematically and comprehensively explored in GBM. Here, we found that decreased FTO expression in clinical specimens correlated with higher glioma grades and poorer clinical outcomes. Functionally, FTO inhibited growth and invasion in GBM cells <i>in vitro</i> and <i>in vivo</i>. Mechanistically, FTO regulated the m⁶A modificationMolecular therapy. Nucleic acidsSPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner.PMC8905236ZR2019BH057ZR2020QH1748190254081702468Xue FLi GPan ZFan YGuo XDeng LWang HNi SZhang SGuo QWang JXu JQiu WZhao SChen ZZhao RJin CWang SQi YGao ZLi BXue HfalseSPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner.As one of the most common post-transcriptional modifications of mRNAs and noncoding RNAs, N⁶-methyladenosine (m⁶A) modification regulates almost every aspect of RNA metabolism. Evidence indicates that dysregulation of m⁶A modification and associated proteins contributes to glioblastoma (GBM) progression. However, the function of fat mass and obesity-associated protein (FTO), an m⁶A demethylase, has not been systematically and comprehensively explored in GBM. Here, we found that decreased FTO expression in clinical specimens correlated with higher glioma grades and poorer clinical outcomes. Functionally, FTO inhibited growth and invasion in GBM cells <i>in vitro</i> and <i>in vivo</i>. Mechanistically, FTO regulated the m⁶A modification2022-01-01T00:00:00Z2022 Mar2025-04-04T23:17:08.808Z2025-04-04T23:17:08.808ZS-EPMC89052363531728310.1016/j.omtn.2021.12.035