MiR-455-3p mediates PPARα through UBN2 to promote apoptosis and autophagy in acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is one of the deadliest hematologic malignancies, and its targeted therapy has developed slowly. The molecular mechanism of the pathophysiology of the disease remains to be clarified. The aim of our study was to probe the specific regulatory mechanism of miR-455-3p in AML. This study measured the levels of miR-455-3p and ubinuclein-2 (UBN2) in AML cell lines, evaluated cell viability with CCK-8, used flow cytometry to estimate the cell cycle and apoptosis, detected cell apoptosis and autophagy-related protein levels by Western blotting, and added 50 µM chloroquine (CQ) to evaluate the relationship between autophagy and AML. In animal experiments, HL-60 cells were injected into male non-obese diabetic/severe combined immunodeficiency disease (NOD/SCID) mice through the tail vein to determine survival time and observe the degree of liver and spleen damage in the mice. miR-455-3p was prominently reduced in the peripheral blood and AML cell lines, and UBN2 showed high expression. The transfected miR-455-3p mimic effectively restrained the activity of AML cells, whereas overexpression of UBN2 or the addition of the autophagy inhibitor CQ reversed the effect of miR-455-3p. The interaction between UBN2 and peroxisome proliferator-activated receptor alpha (PPARα) was confirmed by coimmunoprecipitation, and overexpression of PPARα reversed the promoting effect of UBN2 knockdown on apoptosis and autophagy in AML cells. In conclusion, miR-455-3p mediates PPARα protein expression through UBN2, exacerbating AML cell apoptosis and autophagy. This study found that miR-455-3p plays an important role in AML cell apoptosis and autophagy, which may provide novel insights for the treatment of AML diseases.