miRNA-301a induces apoptosis of chronic myelogenous leukemia cells by directly targeting TIMP2/ERK1/2 and AKT pathways.

We investigated the biological functions and mechanism of miRNA-301a on apoptosis in chronic myelogenous leukemia (CML). The expression of mi RNA-301a in patient with CML cells was higher than the expression of normal patients. Overall survival (OS) of chronic granulocytic leukemia cell patient with low miRNA-301 expression was superior to that of CML patient with high miRNA-301 expression. Moreover, the upregulation of miRNA-301a increased cell proliferation, inhibited apoptosis and caspase-3 and-9 activity of K562 cells. Next, the upregulation of miRNA-301a suppressed Bax/Bcl-2 rate and TIMP2 protein expression, increased phosphorylation-ERK1/2 and decreased phosphorylation-AKT protein expression of K562 cells. Furthermore, si-TIMP2 expression enhanced the upregulation of miRNA-301a on the promotion of cell proliferation, inhibition of apoptosis and caspase-3 and -9 activity, suppression of Bax/Bc1-2 rate, increasing phosphorylation-ERK1/2 and decreasing phosphorylation-AKT protein expression of K562 cells. Taken together, our results clearly suggested that miRNA-301a induces apoptosis of CML cells by directly targeting the TIMP2/ERK1/2 and AKT pathways.