MiR 26 targeting methyltetrahydrofolate reductase inhibits the proliferation of acute myeloid leukemia cells via JAK/STAT pathway

Abstract

Purpose: To investigate the effect of microribonucleic acid (miR)-26 targeting methyltetrahydrofolate reductase (MTHFR) on cell proliferation, cycle, and apoptosis in acute myeloid leukemia (AML).Methods: The expressions of miR-26 in three types of human AML cell lines (HL-60, Kasumi-1, and KG-1a) and normal myeloid cell line (HS-5) were determined via quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR), while the effect of the over-expression of miR-26 on the proliferation, cell cycle and apoptosis of AML cells was evaluated using cell counting kit-8 (CCK-8) assay and flow cytometry. The potential target for miR-26 was predicted using public miRNA database TargetScan, and whether miR-26 binds to the predicted target was determined using a dual-luciferase reporter assay. Western blotting was performed to determine the effect of miR-26 on Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway-associated proteins.Results: Expression level of miR-26 was significantly lower in all AML cell lines than in HS-5 cells (p < 0.05). Overexpression of miR-26 inhibited the proliferation of KG-1a cells, reduced the percentage of cells in S phase, increased those in G0/G1 phase, and enhanced apoptosis of KG-1a cells (p < 0.05). After overexpression of miR-26, protein expression levels of phosphorylated (p)-JAK and p-STAT were down-regulated, while those of JAK and STAT did not change significantly.Conclusion: Expression of miR-26 is down-regulated in AML, while MiR-26 targeting of MTHFR induces apoptosis and cycle arrest of AML cells through the JAK/STAT pathway, thus inhibiting AML cell proliferation in vitro.