PPM1D Knockdown Suppresses Cell Proliferation, Promotes Cell Apoptosis, and Activates p38 MAPK/p53 Signaling Pathway in Acute Myeloid Leukemia.

Abstract

Objectives:This study was to explore the effect of protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown on proliferation and apoptosis as well as p38 MAPK/p53 signaling pathway in acute myeloid leukemia.Methods:The expression of protein phosphatase, Mg2+/Mn2+ dependent 1D was detected in acute myeloid leukemia cell lines including SKM-1, KG-1, AML-193, and THP-1 cells, and normal bone marrow mononuclear cells isolated from healthy donors. The knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D was conducted by transfecting small interfering RNA into AML-193 cells and KG-1 cells.Results:The relative messenger RNA/protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were higher in SKM-1, KG-1, AML-193, and THP-1 cells compared with control cells (normal bone marrow mononuclear cells). After transfecting protein phosphatase, Mg2+/Mn2+ dependent 1D small interfering RNA into AML-193 cells and KG-1 cells, both messenger RNA and protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were significantly reduced, indicating the successful transfection. Most importantly, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D suppressed cell proliferation and promoted cell apoptosis in AML-193 cells and KG-1 cells. In addition, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D enhanced the expressions of p-p38 and p53 in AML-193 cells and KG-1 cells. The above observation suggested that protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown suppressed cell proliferation, promoted cell apoptosis, and activated p38 MAPK/p53 signaling pathway in acute myeloid leukemia cells.Conclusion:Protein phosphatase, Mg2+/Mn2+ dependent 1D is implicated in acute myeloid leukemia carcinogenesis, which illuminates its potential role as a treatment target for acute myeloid leukemia.