Li Yan, Zhao Lifen, Li Nana, Miao Yuan, Zhou Huimin, Jia Li
Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
Oncol Rep. 2017 Apr;37(4):2193-2200. doi: 10.3892/or.2017.5464. Epub 2017 Feb 17.
Multidrug resistance (MDR) is commonly correlated with the poor prognosis of chronic myelogenous leukemia. Aberrant expression of microRNAs (miRNAs) plays an important role in the MDR of various types of cancers. MicroRNA-9 (miR-9) has been confirmed to be dysregulated in many types of cancers. However, the relationship between miR-9 and MDR in chronic myelogenous leukemia (CML) remains largely unknown. In the present study, we showed that miR‑9-3p (miR-9) was downregulated in adriamycin (ADR)‑resistant K562/ADR cells and CML/MDR patients. Overexpression of miR-9 was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitized tumors to chemotherapy in vivo. Furthermore, we found that ABCB1 is a direct target of miR-9. These findings suggest that miR-9 plays a critical role in MDR in CML by targeting ABCB1. These results provide new evidence of miR-9 as a biomarker for clinical diagnosis and as a potential therapeutic target for CML.
多药耐药(MDR)通常与慢性髓性白血病的不良预后相关。微小RNA(miRNA)的异常表达在各类癌症的多药耐药中起重要作用。微小RNA-9(miR-9)已被证实在多种癌症中表达失调。然而,miR-9与慢性髓性白血病(CML)多药耐药之间的关系仍 largely未知。在本研究中,我们发现miR-9-3p(miR-9)在阿霉素(ADR)耐药的K562/ADR细胞和CML/MDR患者中表达下调。miR-9的过表达足以在体外逆转癌细胞对多种化疗药物的耐药性,并使体内肿瘤对化疗敏感。此外,我们发现ABCB1是miR-9的直接靶点。这些发现表明,miR-9通过靶向ABCB1在CML的多药耐药中起关键作用。这些结果为miR-9作为临床诊断生物标志物和CML潜在治疗靶点提供了新证据。