Apoptosis induction in acute promyelocytic leukemia cells through upregulation of CEBPα by miR-182 blockage

Document Type : Original article

Authors

1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

3 Department of Immunology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran

Abstract

MicroRNAs (miRNAs) involved in regulation of the genes. The CCAAT/enhancer-binding protein-α (CEBPα) is a crucial transcription factor for normal hematopoiesis and cell cycle that frequently disrupted in human acute myeloid leukemia (AML). The miR-182 up-regulation in several malignant diseases such as AML was reported, in the other hand bioinformatics analysis revealed CEBPα targeted by miR-182.miR-182-5p inhibition in human acute promyelocytic leukemia (APL) cell line was performed by using locked nucleic acid (LNA) and subsequently miR-182-5p and CEBPα expression, apoptosis, necrosis and cell proliferation were measured.After LNA-anti-miR-182-5p transfection to cells at different time points, miR-182-5p down regulation and CEBPα overexpression was revealed in the LNA-anti-miR group compared to the control groups. The cell viability was meaningfully varied between LNA-anti-miR and control groups. Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia.

Keywords

References

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