Up-Regulation of miR-625-5p Correlates with Suppressed Sox2, Increased Apoptosis, and Cell Cycle Arrest via The PI3K/AKT Signalling Pathway in Acute Myeloid Leukaemia

Kangup Steven  Kereka; Seyed Hadi  Mousavi; Shaban  Alizadeh; Leila  Ghaemmaghami; Ghasem  Fakoorizad; Jamal  Motallebzadeh Khanmiri

doi:10.18502/ijhoscr.v18i4.16760

Kangup Steven Kereka Department of Haematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
Seyed Hadi Mousavi Department of Haematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
Shaban Alizadeh Department of Haematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
Leila Ghaemmaghami Islamic Azad University, North Tehran Branch, Iran
Ghasem Fakoorizad Department of Haematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
Jamal Motallebzadeh Khanmiri Department of Haematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijhoscr.v18i4.16760

Keywords: Acute myeloid leukaemia; PI3K/AKT signaling pathway; miR-625; Sox2; Proliferation

Abstract

Background: Up-regulation of the microRNA-625 and abnormal expression of the Sox2 gene have been studied and seen in several tumors. Few reports have also shown the aberrant expression of miR-625 and Sox2 expression in various cancers. Several studies have also confirmed that phosphatidylinositol 3' -kinase /protein kinase B pathways regulate hematological malignancies, including Acute Myeloid Leukemia (AML). Thus, this study aimed to investigate the effects of mir-625 up-regulation on proliferation, apoptosis, and cell cycle by targeting the Sox2 gene via the downstream Akt signaling pathway and cell cycle regulators, such as p21, p27, and cyclin E in the KG-1 cell line.

Materials and Methods: Cells obtained from the KG-1 cell line were cultured and transfected with plasmid DNA (miR-625) and scrambled as the control using the Lonza electroporation system. Flow cytometry was used to evaluate cell cycle, proliferation, and apoptosis. Relative gene expression was validated by qRT-PCR. All data were analyzed using graph pad prism 7.01 and REST 2009.

Results: KG-1 cells transfected with the mir625-GFP construct showed decreased proliferation, increased apoptosis, and induced cell cycle arrest. Low levels of Sox2, p21, cyclin E, and up-regulation of p27 were confirmed and validated by qRT-PCR ( P < 0.05 ).

Conclusion: MiR-625 can be a promising approach to aid in the treatment of AML. However, further studies are required in this field