miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis. 
Ara-C is one of the most commonly used drugs in the treatment of AML.  However, the development of drug resistance always prevented its further use.  It has been shown that miR-181a is associated with the clinical outcome of AML patients.  Here, we investigated the possible role of miR-181a in AML Ara-C resistance.  miR-181a expression was measured by real-time PCR.  Cell viability was detected by MTT assay.  Protein expressions were measured by western blotting.  Caspase activity was examined by fluorescence assay.  We found that miR-181a expression was downregulated in the Ara-C-resistant cell line HL-60/Ara-C compared with its parental cell line HL-60.  Overexpression of miR-181a in HL-60/Ara-C cells sensitized the cells to Ara-C treatment.  Furthermore, Bcl-2 was confirmed as a direct miR-181a target by immunoblot analysis and reporter gene assays.  Knockdown of Bcl-2 mimicked the effect of enforced miR-181a expression by reducing cell viability.  In addition, the apoptosis pathway was activated by cytochrome C release and caspase 9/caspase 3 activation after miR-181a overexpression.  This study for the first time demonstrated that downregulation of miR-181a and upregulation of Bcl-2 in leukaemia cells confer resistance to Ara-C-based therapy.  These results suggest that restoration of miR-181a expression might provide a promising therapeutic in drug resistance of leukaemia.