MiR-744 mediates the Oxaliplatin chemoresistance in colorectal cancer through inhibiting BIN1

Yu Zhou, Anjiang He, Lei Zhang,  Gangfeng Yi

Abstract:

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. However, lacking of novel and sensitive chemotherapy revealed the major challenge to improve the survival of CRC patients. The aim of this study was to explore the effect and mechanism of miR-744 on the oxaliplatin chemoresistance in CRC. Firstly, the levels of miR-744 were elevated significantly in CRC tissues from patients with oxaliplatin administration before surgery and in oxaliplatin-resistant HCT116 cells. Then, the oxaliplatin chemoresistance was enhanced by miR-744 overexpression, while was attenuated by miR-744 inhibition in HCT116 and T84 cells. Additionally, the level of BIN1 protein was found to be regulated negatively by miR-744, and BIN1 overexpression blocked the oxaliplatin chemoresistance induced by miR-744. Furthermore, BIN1 was proved to be a direct target of miR-744 by luciferase reporter assay. Taken together, these findings demonstrated that miR-744 might positively mediate the oxaliplatin chemoresistance through suppressing BIN1 expression in CRC cells, thus suggested a rationale target for the developing more effective strategies to reverse oxaliplatin resistance in CRC treatment.