Inhibition of c-MYC-miRNA 19 Pathway Sensitized CML K562 Cells to Etoposide via NHE1 Upregulation

As a previously discovered target of DNA damage, Na(+)/H(+) exchanger 1 (NHE1) plays a role in regulation of intracellular pH (pH(i)) through the extrusion of intracellular proton (H(+)) in exchange for extracellular sodium (Na(+)). Its abnormal expression and dysfunction have been reported in solid tumor and hematopoietic malignancies. Here, we reported that suppression of NHE1 in BCR-ABL(+) hematopoietic malignancies' K562 cells treated with Etoposide was manipulated by miR-19 and c-MYC. Inhibition of miR-19 or c-MYC enhanced the expression of NHE1 and sensitized K562 cells to Etoposide in vitro. The in vivo nude mouse transplantation model was also performed to confirm the enhanced sensitivity of K562 cells to Etoposide by inhibiting the miR-19 or c-MYC pathway. TCGA analysis conferred a negative correlation between miR-19 level and leukemia patients' survival. Thus, our results provided a potential management by which the c-MYC-miRNA 19 pathway might have a crucial impact on sensitizing K562 cells to Etoposide in the therapeutic approaches.