MicroRNA-221 sensitizes chronic myeloid leukemia cells to imatinib by targeting STAT5

Abstract

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:

• miR-221
• ; STAT5
• ; drug-resistance
• ; chronic myeloid leukemia

Acknowledgements

We thank all the teachers in the Central Laboratory of Anhui Provincial Hospital for their passionate help and technical support.

Potential conflict of interest

Disclosure forms provided b the author are available with the full text of this article at https://doi.org/10.1080/10428194.2018.1543875

Table 1. Primers used for quantitative real-time PCR analysis.

Additional information

Funding

This study was supported by a grant from the Anhui Provincial Natural Science Foundation (grant number 1708085MH223).