MicroRNA-181a and its target Smad 7 as potential biomarkers for tracking child acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic tumor. MiR-181a was expected to have a role in the development of hematological malignancies; it might act as tumor suppressor or oncogene. Smad7 was selected as miR-181a target pair. It is a negative regulator for the TGF-β1 signaling pathway. In this study, relative expression levels of miR-181a by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), both Smad 7 and TGF-β1 proteins levels by enzyme linked immunosorbent assay (ELISA) were all measured in serum of 60 child, 30 with ALL and 30 age and sex matched healthy child as control group. MiR-181a expression showed highly significant decrease; plus a significant increase and decrease of Smad7 and TGF-β1 protein levels respectively, in serum samples of ALL as compared to control group. MiR-181a expression achieved a highly significant positive and a significant negative correlation with TGF-β1 and Smad7 respectively. Furthermore, the levels of Smad7 and TGF-β1 were negatively correlated with each other (p<0.05). Although, positivity rate of both Smad7 and TGF-β1 in ALL group increased with presence of hepatosplenomegaly, still there was no statistical significance. In conclusion, miR-181a could act as a tumor suppressor in pediatric ALL with over expression of its target pair, Smad7. Smad7 regulates TGF-β1 signaling via a negative feedback loop and mediates the interaction between TGF-β1 and other signaling pathways; suggesting that Smad7 over expression may have therapeutic potential in ALL.