RNA‐binding protein PUM2 promotes T‐cell acute lymphoblastic leukemia via competitively binding to RBM5 3′UTR with miR‐28‐5p

Abstract Objective T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematologic malignancy, and T‐ALL patients are prone to early disease relapse and suffer from poor outcomes. The crucial function of RNA‐binding proteins (RBPs) has been reported in the progression of cancers by regulating the expression of transcripts. This study aimed to reveal the role and molecular regulatory mechanism of RBP Pumilio2 (PUM2) in T‐ALL. Methods The expression of genes was detected by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis. The viability, proliferation, and apoptosis of T‐ALL cells were evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, 5‐ethynyl‐2′‐deoxyuridine, and flow cytometry analysis. Luciferase reporter, RNA pulldown, and RNA immunoprecipitation assays were performed to confirm the binding of PUM2 to RBM5. The combination between RNA‐binding motif protein 5 (RBM5) and microRNA (miR)‐28‐5p was validated using luciferase reporter assay. Results Our data revealed that PUM2 was highly expressed in T‐ALL blood samples and cell lines. PUM2 knockdown suppressed the proliferation but accelerated the apoptosis of T‐ALL cells in vitro. Additionally, RBM5 exhibited a low expression level in T‐ALL samples and cells. PUM2 negatively regulated RBM5 via targeting its 3′untranslated region (3′UTR). Moreover, PUM2 competitively bound to RBM5 3′UTR with miR‐28‐5p. Rescue experiments showed that RBM5 knockdown reversed the anti‐tumor effects mediated by PUM2 knockdown in T‐ALL cells. Conclusion PUM2 plays as a novel oncogenic RBP in T‐ALL by competitively binding to RBM5 mRNA with miR‐28‐5p.