The effect of Genistein on miRNA biogenesis pathway genes (Dicer and AGO2) expression in Acute Lymphoblastic Leukemia (ALL)

Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, accounting for one third of the cancers of this age. It results from genetic and environmental factors. miRNAs considered as a causative agents of this cancer that have recently been considered. Generally, changing in miRNA expression can play a critical role in main important pathways in cells. Therefore, it can be hypothesizied that genes involved in miRNAs biogenesis pathways (e.g. Dicer and AGO2) can play in cancers. Afew studies has been reported for Genistein effect on ALL. Objective: This study evaluated the expression of the cytoplasmic genes of miRNA biogenesis pathways in patients with ALL, and also the Genistein effect on the expression of these genes in the cell lines of this cancer. Methods: 25 human cases with ALL and 25 healthy controls were used to evaluate the expression of AGO2 and Dicer expressions. In this study, four groups of ALL cell lines (Jurkat, Molt4, Molt17 and Naml6) were used for Genistein treatment. 15, 30, and 60 μM doses of Genistein were used. Dicer and AGO2 mRNA expression levels were evaluated after 24 and 48 hours by Real time-PCR. In order to determine the apoptosis of the cells, a flow cytometry was placed at that time. Results: This study indicate that genistein can decrease the number of live cells and increase the mortality rate (P <0.05). The concentration of 60μM resulted in the highest mortality rate in all cell lines. Expression levels of Dicer and AGO2 in patients compared to healthy controls increased and decreased respectively (P <0.05). Ginstein increased the Dicer expression in both the Naml6 and Molt17 cell lines significantly, but in two other cell lines, expression changes due to Genistein effect were not significant (P> 0.05). In the present study the increase of AGO2 gene expression after the effect of Genistein compared to the untreated group in all cell lines was statistically significant (P <0.05). Discussion: The findings indicated that genistein increases the apoptosis and death rate in ALL cells through probably changing on the expression of Dicer and AGO2. It is possible to consider the inhibiting role for genistein in cell growth through effects on the cell cycle. Anyway, in future studies, it is better to examine human in order to determine the clinical effects. Also, by comparing the findings from gene expression in human specimens and cell samples, it can be concluded that genistein can play an inhibiting role in cell cycle pathways and also increasing apoptosis by increasing the expression of AGO2 as a mediator. Keywords: genistein; Dicer; AGO2; leukemia, ALL