SPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner
Shouji Zhang, Shulin Zhao, Yanhua Qi, Boyan Li, Huizhi Wang, Ziwen Pan, Hao Xue, Chuandi Jin, Wei Qiu, Zihang Chen, Qindong Guo, Fan Yang, Jianye Xu, Zijie Gao, Shaobo Wang, Xing Guo, Linhong Deng, Shilei Ni, Fuzhong Xue, Jian Wang, Rongrong Zhao, Gang Li
Abstract
A 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.