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The relapse and resistance to cytarabine (Ara-C) therapy is still a dominating obstacle to the successful clinical treatment of acute myeloid leukemia (AML). Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells to anticancer drugs; yet, the mechanism is not fully understood. In this study, we showed a significant downregulation of miR-134 in human multidrug-resistant leukemia cells and relapsed/refractory AML patient samples. Overexpression of miR-134 sensitized K562/A02 and HL-60/ADM cells to Ara-C, inhibited cell colony formation, and enhanced the ability of Ara-C to induce apoptosis. Mechanistic analyses revealed that Mnks was a putative target of miR-134, which was inversely correlated with miR-134 expression in human multidrug-resistant leukemia cells and relapsed/refractory AML patient samples. Further investigation showed that miR-134 increased the anti-tumor effects of Ara-C through inhibiting phosphorylation of eukaryotic initiation factor 4E and downregulating Mcl-1 and bcl2, which was independent of p38 and Erk1/2 activation. Taken together, our results demonstrate that miR-134 plays a pivotal role in AML Ara-C resistance through increasing cell sensitivity to Ara-C and promoting apoptosis by targeting Mnks.

miR-134 increases the antitumor effects of cytarabine by targeting Mnks in acute myeloid leukemia cells