MicroRNAs (miRNAs) are involved in various processes from the development to drug resistance of tumors, including chronic myeloid leukemia (CML). In this study, we examined the STAT5-related miRNA-expression profile in CML cell lines (K562 and imatinib-resistant K562/G) by quantitative real-time reverse-transcriptase polymerase chain reactions. MiR-221 expression was markedly decreased in K562/G cells and peripheral blood mononuclear cells from patients with treatment failure, when compared to imatinib-sensitive CML cells and patients with optimal responses respectively. We also observed the expression of STAT5 inversely correlated with miR-221 expression in K562 and KBM5 cells. Additionally, STAT5 was validated as a direct target of miR-221 in dual-luciferase reporter vector assays. MiR-221 restoration and STAT5 knockdown in K562/G cells increased the sensitivity of CML cells to imatinib by reducing the Bcl2: Bax ratio. Collectively, our data suggested that miR-221-STAT5 axis played crucial roles in controlling the sensitivity of CML cells to imatinib.
Keywords: STAT5; chronic myeloid leukemia; drug-resistance; miR-221.