Phosphatase of regenerating liver-3 is regulated by signal transducer and activator of transcription 3 in acute myeloid leukemia.

Overexpression of protein-tyrosine phosphatase of regenerating liver 3 (PRL-3) has been identified in about 50% of patients with acute myeloid leukemia (AML). The mechanism of regulation of PRL-3 remains obscure. Signal transducer and activator of transcription 3 a latent transcriptional factor, has also been often found to be activated in AML. We first identified sites in the promoter of PRL-3 genes. Then we experimentally validated the direct binding and transcriptional activation. We applied shRNA-mediated knockdown and overexpression approaches in liver cells and leukemic cells to validate the functional regulation of PRL-3 by A core signature, derived through data mining from publicly available gene expression data, was employed to correlate PRL-3 expression in large AML patient samples. We discovered that duanyu18133 binds to the -201 to -210 region of PRL-3, which was conserved between human and mouse. Importantly, PRL-3 protein was significantly reduced in mouse liver cells compared with type counterparts, and ectopic expression of duanyu18133 in these cells led to a pronounced increase in PRL-3 protein. We demonstrated that duanyu18133 functionally regulated PRL-3, and duanyu18133 core signature was enriched in AML with high PRL-3 expression. Targeting either duanyu18133 or PRL-3 reduced leukemic cell viability. Silencing PRL-3 impaired invasiveness and induced leukemic cell differentiation. In conclusion, PRL-3 was transcriptionally regulated by duanyu18133. The regulatory loop contributes to the pathogenesis of AML, and it might represent an attractive therapeutic target for antileukemic therapy.

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