Gene Regulation
Transforming Growth Factor β Mediates Drug Resistance by Regulating the Expression of Pyruvate Dehydrogenase Kinase 4 in Colorectal Cancer
Drug resistance is one of the main causes of colon cancer recurrence. However, our understanding of the underlying mechanisms and availability of therapeutic options remains limited. Here we show that expression of pyruvate dehydrogenase kinase 4 (PDK4) is positively correlated with drug resistance of colon cancer cells and induced by 5-fluorouracil (5-FU) treatment in drug-resistant but not drug-sensitive cells. Knockdown of PDK4 expression sensitizes colon cancer cells to 5-FU or oxaliplatin-induced apoptosis in vitro and increases the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo.MicroRNA-520g Confers Drug Resistance by Regulating p21 Expression in Colorectal Cancer
Background: MicroRNAs are small non-protein-coding RNAs that inhibit target gene expression.Results: p53 suppresses miR-520g expression, and miR-520g mediates drug resistance through down-regulation of p21 expression.Conclusion: The p53/miR-520g/p21 signaling axis plays an important role in the response of colorectal cancer to chemotherapy.Significance: Our study identifies miR-520g as a potential target against drug resistance in colorectal cancer, especially in patients with mutant p53.
