RUNX1 interacts with lncRNA SMANTIS to regulate monocytic cell functions [RNA_THP1_diff_OCL]
Monocytes are important for acute myeloid leukemia (AML), but the influence of long non-coding RNAs (lncRNAs) in this context is unknown. Previously we demonstrated that lncRNA SMANTIS maintains endothelial angiogenic functions and endothelial-monocyte adhesion. Here, the role of SMANTIS in monocytes was examined. SMANTIS was higher expressed in monocytes than in endothelial cells, lost in macrophages, and varied in patients with different AML subtypes. Interaction studies revealed that SMANTIS binds RUNX1, a transcription factor frequently mutated in AML, primarily through its Alu-element. RNA-seq after CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1 revealed an association with cell adhesion and both limited the monocyte adhesion to endothelial cells. Mechanistically, SMANTIS KO reduced RUNX1 genomic binding, and interfered the interaction of RUNX1 with EP300. Collectively, SMANTIS interacts with RUNX1 and limits cell adhesion, which may thus offer a novel therapeutic strategy for AML. Overall design: RNA sequencing (n = 2) of THP-1, an accepted human leukemia monocytic cell line. LentiCRISPRv2-mediated knockouts were generated using a dual-guide RNA (gRNA) system approach to knockout SMANTIS, and a single gRNA approach to knock out RUNX1.For the non-target control (NTC) also a single gRNA approach was used.