MiRNA-409-5p dysregulation promotes imatinib resistance and disease progression in children with chronic myeloid leukemia

Y.-Y. Liu, W.-Y. Jiao, T. Li, Y.-Y. Bao

Department of Hematology, The First People’s Hospital of Hefei City, Hefei, China. jywm45@163.com

---

• Hematology

OBJECTIVE: To elucidate the role of miRNA-409-5p in the pathogenesis of child chronic myeloid leukemia (CML) and its potential mechanism.

PATIENTS AND METHODS: Expression levels of miRNA-409-5p and NUP43 in peripheral blood of CML children and healthy controls were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and flow cytometry were conducted to evaluate the regulatory effect of miRNA-409-5p on proliferative potential and cell cycle progression of CML cells. Protein levels of PCNA, c-Myc, and cyclin D1 in CML were examined by Western blot. Dual-luciferase reporter gene assay verified the binding of target gene NUP43 to miRNA-409-5p. Finally, the potential effect of miRNA-409-5p on Imatinib resistance in CML was elucidated.

RESULTS: Compared with healthy children, miRNA-409-5p expression in peripheral blood of CML children markedly decreased. Similarly, miRNA-409-5p expression was lower in CML cells. Contrary to the expression pattern of miRNA-409-5p, NUP43 was highly expressed in CML. The miRNA-409-5p overexpression remarkably inhibited proliferative potential and arrested cell cycle in the G0/G1 phase. Protein levels of PCNA, c-Myc, and cyclin D1 were downregulated in CML cells overexpressing miRNA-409-5p. The knockdown of miRNA-409-5p obtained the opposite trends. NUP43 was proved to be the target gene of miRNA-409-5p and negatively regulated by miRNA-409-5p. After overexpression of miRNA-409-5p, Imatinib treatment elevated proliferation inhibition and cell cycle arrest of K562 and KG-1a cells.

CONCLUSIONS: MiRNA-409-5p is lowly expressed in child CML, which inhibits proliferative potential and cell cycle progression by upregulating NUP43 expression. In addition, miRNA-409-5p overexpression enhances Imatinib resistance in CML.

Free PDF Download