GSE240582 Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [meRIP-Seq]

Contributors : Monica M Pomaville ; Mohansrinivas Chennakesavalu ; Pingluan Wang ; Zhiwei Jiang ; Hui-Lung Sun ; Peizhe Ren ; Ryan Borchert ; Varsha Gupta ; Chang Ye ; Ruiqi Ge ; Zhongyu Zhu ; Mallory Brodnik ; Yuhao Zhong ; Kelley Moore ; Helen Salwen ; Rani E George ; Malgorzata Krajewska ; Alexandre Chlenski ; Mark A Applebaum ; Chuan He ; Susan L CohnSeries Type : OtherOrganism : Homo sapiensThe N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3 and METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype were associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation and increased stability and expression of target mRNAs. In preclinical studies, STM2457 treatment suppressed the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research