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mA Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.

Cancer Cell. 2017; 
ZhangSicong,ZhaoBoxuan Simen,ZhouAidong,LinKangyu,ZhengShaoping,LuZhike,ChenYaohui,SulmanErik P,XieKeping,BöglerOliver,MajumderSadhan,HeChuan,HuangS
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Gene Synthesis ALKBH5 expression plasmid was generated by cloning the full-length ORF of human ALKBH5 gene (NM_017758.3) into pcDNA3.1-DYK vector (GenScript). ALKBH5 H204A was generated by GenScript. pcDNA3.1-DYK-HuR was generated by GenScript. ALKBH5 and HuR were cloned to pcDNA3.1 vector without tag. Get A Quote

摘要

The dynamic and reversible N-methyladenosine (mA) RNA modification installed and erased by N-methyltransferases and demethylases regulates gene expression and cell fate. We show that the mA demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and mA-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ... More

关键词

ALKBH5,FOXM1,glioblastoma,m(6)A modifica