BioProject

Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and is involved in various cellular processes, including cancer development. More...

Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and is involved in various cellular processes, including cancer development. PRMT2 expression is increased in several cancer types although its role in acute myeloid leukemia (AML) remains unknown. Here, we investigate the role of PRMT2 in a cohort of patients with AML, PRMT2 knockout AML cell lines as well as a Prmt2 knockout mouse model. In patients, low PRMT2 expressors are enriched for inflammatory signatures, including the NF-κB pathway, and show inferior survival. In keeping with a role for PRMT2 in control of inflammatory signaling, bone marrow-derived macrophages from Prmt2 KO mice display increased pro-inflammatory cytokine signaling upon LPS treatment. In PRMT2-depleted AML cell lines, aberrant inflammatory signaling has been linked to overproduction of IL6, resulting from a deregulation of the NF-κB signaling pathway, therefore leading to hyperactivation of STAT3. Together, these findings identify PRMT2 as a key regulator of inflammation in AML. Overall design: To investigate the functions of PRMT2 in AML, we used the CRISPR-Cas9 editing strategy on the HL-60 cells to generate stable PRMT2 knockout AML cell lines. We performed single-cell sorting on edited cells. Then, PRMT2 gene and protein expressions were screened on all the clones. The best KO clones (named 'AA13' and AA14') were selected and prepared for bulk RNA-sequencing, as well as the wild type (WT) HL-60 cell line as a control. All 3 samples were run on triplicates. Less...