The Effect of Decitabine on the Expression and Methylation of the PPP1CA in Association with Changes in miR-181b in NALM6 Cell Line

Precursor B-cell acute lymphoblastic leukemia(B-ALL) is the most widespread pediatric malignancy and is a highly diverse disease characterized by cytogenetic and molecular abnormalities, including altered microRNA (miRNA) expression signatures. DNA methylation and modifications in the microRNAs expression are identified to be significant reasons for B-ALL. Decitabine as a DNA methyltransferase inhibitor agent is able to provoke hypomethylation in various tumor suppressor genes. Much proof has shown PPP1CA act as a tumor suppressor gene in numerous malignancies. In the current research, the mRNA expression of PPP1CA gene using qReal-time PCR in Nalm6 cell line and five patients suffer from ALL with mean age 5.6 years were determined in comparison with seven normal healthy donors age and sex-matched. Quantitative Real-time PCR investigation exhibited that the expression level of PPP1CA gene was significantly reduced in Nalm6 and according to the Methylation-specific PCR (MSP) analysis, this gene was hypermethylated in Nalm6. In the next step, the effects of decitabine treatment on the methylation and expression of this gene in association with changes in miR-181b expression levels were assessed in an optimal concentration of 2.5 μM of decitabine. Our data confirmed that decitabine is capable to restore the expression level of the mentioned gene and down-regulate expression level of oncomir 181b in the Nalm6 cell line. Consequently, it appears that decitabine can be utilized as a potential drug for the first-line treatment of B-ALL patients, but further in vivo study is required.