MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer [Cell Biology]

January 23rd, 2015 by Zhang, Y., Geng, L., Talmon, G., Wang, J.

Development of drug resistance is one of the major causes of colorectal cancer recurrence yet mechanistic understanding and therapeutic options remain limited. Here we show that expression of microRNA (miR)-520g is correlated with drug resistance of colon cancer cells. Ectopic expression of miR-520g confers resistance to 5-fluorouracil (5-FU) or oxaliplatin-induced apoptosis in vitro and reduces the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-520g mediates drug resistance through down-regulation of p21 expression. Moreover, p53 suppresses miR-520g expression and that deletion of p53 up-regulates miR-520g expression. Inhibition of miR-520g in p53-/- cells increases their sensitivity to 5-FU treatment. Importantly, studies of patient samples indicate that expression of miR-520g correlates with chemoresistance in colorectal cancer. These findings indicate that the p53/miR-520g/p21 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of miR-520g or restoration of p21 expression may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, especially in those with mutant p53.