PTBP1 Facilitates Acute Myeloid Leukemia Cell Migration, Invasion, and Expression of EMT Markers by Regulating WNK1

Acute myeloid leukemia (AML) is an aggressive and molecularly diverse hematologic malignancy with unfavorable clinical outcomes and limited options for targeted therapy. This study investigated whether polypyrimidine tract-binding protein 1 (PTBP1), an RNA-binding protein (RBP), affects AML progression by binding to WNK lysine-deficient protein kinase 1 (WNK1).

We first determined the level of WNK1 in AML using the Gene Expression Profiling Interactive Analysis‌ (GEPIA) database and verified it by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) assay. AML cell migration and invasion were analyzed using Transwell assays following WNK1 modulation. Epithelial-to-mesenchymal transition (EMT) marker level was confirmed by WB assay. The influence of WNK1 on the in vivo metastasis of AML was verified via tail vein injection of WNK1-knockdown AML cells into Non-Obese Diabetic/Severe Combined Immunodeficiency (NOD/SCID) mice. Mechanistically, RNA pull-down and RNA immunoprecipitation (RIP) assays were utilized to interpret the relationship between PTBP1 and WNK1 and to determine whether PTBP1 affects AML cell migration and invasion by regulating WNK1, using rescue experiments.

WNK1 was highly expressed in AML. WNK1 inhibition hindered AML cell migration, invasion, and the expression of EMT markers. WNK1 depletion markedly suppressed the metastasis of AML cells in vivo. Mechanistically, PTBP1 directly bound to WNK1 and increased its mRNA stability. Furthermore, PTBP1 facilitated AML cells migration, invasion, and the expression of EMT markers via WNK1.

We demonstrate that PTBP1 promotes AML progression by modulating WNK1. PTBP1 may therefore represent a potential therapeutic target in AML.