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dc.contributor.authorZhang, Shouji
dc.contributor.authorZhao, Shulin
dc.contributor.authorQi, Yanhua
dc.contributor.authorLi, Boyan
dc.contributor.authorWang, Huizhi
dc.contributor.authorPan, Ziwen
dc.contributor.authorXue, Hao
dc.contributor.authorJin, Chuandi
dc.contributor.authorQiu, Wei
dc.contributor.authorChen, Zihang
dc.contributor.authorGuo, Qindong
dc.contributor.authorFan, Yang
dc.contributor.authorXu, Jianye
dc.contributor.authorGao, Zijie
dc.contributor.authorWang, Shaobo
dc.contributor.authorGuo, Xing
dc.contributor.authorDeng, Lin
dc.contributor.authorNi, Shilei
dc.contributor.authorXue, Fuzhong
dc.contributor.authorWang, Jian
dc.contributor.authorZhao, Rongrong
dc.contributor.authorLi, Gang
dc.description.abstractAs 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 in vitro and in vivo. Mechanistically, FTO regulated the m6A modification of primary microRNA-10a (pri-miR-10a), which could be recognized by reader HNRNPA2B1, recruiting the microRNA microprocessor complex protein DGCR8 and mediating pri-miR-10a processing. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor SPI1, which could be specifically disrupted by the SPI1 inhibitor DB2313. Treatment with this inhibitor restored endogenous FTO expression and decreased GBM tumor burden, suggesting that FTO may serve as a novel prognostic indicator and therapeutic molecular target of GBM.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleSPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manneren_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.source.journalMolecular Therapy - Nucleic Acidsen_US
dc.identifier.citationMolecular Therapy - Nucleic Acids. 2022, 27, 699-717.en_US

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal