FTO promotes multiple myeloma progression by posttranscriptional activation of HSF1 in an m⁶A-YTHDF2-dependent manner.

ABSTRACT: N⁶-methyladenosine (m⁶A), as the most pervasive internal modification of eukaryotic mRNA, plays a crucial role in various cancers, but its role in multiple myeloma (MM) pathogenesis has not yet been investigated. In this study, we revealed significantly decreased m⁶A methylation in plasma cells (PCs) from MM patients and showed that the abnormal m⁶A level resulted mainly from upregulation of the demethylase fat mass and obesity-associated protein (FTO). Gain- and loss-of-function studies demonstrated that FTO plays a tumor-promoting and pro-metastatic role in MM. Combined m⁶A and RNA sequencing (RNA-seq) and subsequent validation and functional studies identified heat shock factor 1 (HSF1) as a functional target of FTO-mediated m⁶

SUBMITTER: Xu A 

PROVIDER: S-EPMC8899603 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature