miRNA-1 promotes acute myeloid leukemia cell pathogenesis through metabolic regulation

Abstract

Graphical AbstractWe blocked pyruvate entry into mitochondria and decreased Oxidative Phosphorylation (OXPHOS) in human AML cell lines MV4-11 and MOLM-14 by using gene editing tools. This metabolic shift led to increased expression of miR-1 in the human AML cell lines. TARGET and TCGA AML patient sample dataset analysis revealed that miR-1 is overexpressed in patients with FLT3-ITD + mutation, and independently from FLT3-ITD, high levels of miR-1 also correlates with reduced survival. Transcriptional and metabolic profiling of miR-1 overexpressing AML cells revealed that miR-1 promotes OXPHOS through glutaminolysis. Moreover, the overexpression of miR-1 in AML cells exacerbated disease in a mouse xenograft model. Together, our work expands current knowledge within the field by uncovering novel connections between AML cell metabolism and miRNA expression that facilitates disease progression. Created with BioRender.com.