Targeted regulation of FoxO3ap/p27Kip1 by miR-155 for mediating HL-60 leukemia cell proliferation and apoptosis

Leukemia patients had significantly elevated miR-155 expression. P27Kip1 plays a role in regulating cell proliferation, cycle and apoptosis. Down-regulation of p27Kip1 participates in leukemia pathogenesis. Transcription factor FoxO3a plays a role in regulating target gene p27Kip1 and is related with leukemia occurrence. Bioinformatics analysis revealed targeted regulation of FoxO3a by miR-155. This study investigated if miR-155 played a role in regulating FoxO3a/p27Kip1 and leukemia pathogenesis. A total of 48 acute promyelocytic leukemia (APL) patients in our hospital were recruited in parallel with 55 healthy individuals. Expressions of miR-155, FoxO3a and p27Kip1 were measured in peripheral monocytes. In vitro cultured APL cell HL-60 was treated with miR-155 inhibitor and/ or pIRES2-FoxO3a. qRT-PCR was used to test expressions of miR-155, FoxO3a and p27Kip1 genes, whilst Western blot was used to test protein level of FoxO3a and p27Kip1, followed by flow cytometry to detect Ki-67 expression and cell apoptosis. APL patients had significantly lower expression of FoxO3a or p27Kip1 in peripheral monocytes, plus significantly elevated miR-155 expression. Dual luciferase assay confirmed the targeted regulation of FoxO3a by miR-155. Over-expression of miR-155 inhibited expression of FoxO3a and downstream regulator factor p27Kip1, and meanwhile inhibited HL-60 cell proliferation to facilitate apoptosis. MiR-155 targets and inhibits expression of FoxO3a and downstream factor p27Kip1, facilitates HL-60 cell proliferation and inhibits cell apoptosis.