ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing m⁶A-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype.

ABSTRACT: N6-methyladenosine (m⁶A) is the most prevalent modification to RNA in higher eukaryotes. ALKBH5 is an RNA demethylase that impacts RNA export and metabolism, and its aberrant expression is associated with the generation of tumours. In this study, we found that ALKBH5 was highly expressed in both primary CD138⁺ plasma cells isolated from multiple myeloma (MM) patients and MM cell lines. Downregulation of ALKBH5 inhibited myeloma cell proliferation, neovascularization, invasion and migration ability, and promoted the apoptosis in vivo and in vitro. MeRIP-seq identified the SAV1 gene as main target gene of ALKBH5. Inhibiting ALKBH5 in MM cells increased SAV1 m⁶A levels, decreased SAV1 mRNA stability and expression, suppressed the stem cell related HIPPO

SUBMITTER: Yu T 

PROVIDER: S-EPMC8990482 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature