Imatinib (IM) has been applied to the chronic phase of chronic myeloid leukemia (CML) and has great benefit on the prognosis of patients with CML. The function of drug efflux mediated by multidrug resistance protein-1 (MDR1) is considered as a main reason for IM drug resistance in CML cells. However, the exact mechanisms of MDR1 modulation in IM resistance of CML cells remain unclear. In the present study, long noncoding RNA (lncRNA) UCA1 was identified as an important modulator of MDR1 by a model system of leukemia cell lines with a gradual increase of MDR1 expression and IM resistance. Overexpression of UCA1 increased MDR1 expression to promote IM resistance of CML cells. Furthermore, for the first time, we demonstrated that UCA1 functions as a competitive endogenous (ceRNA) of MDR1 through completely binding the common miR-16. UCA1-MDR1 might be a novel target for enhancing the therapeutic efficacy of CML patients with IM resistance.
Keywords: MDR1; UCA1; imatinib resistance; lncRNA; miR-16.