miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

Abstract

Gastric cancer (GC) is one of the most common types of malignant cancer worldwide, however improvements are required to the current therapies for GC. Although paclitaxel is one of the most promising chemotherapeutic agents in clinical use for GC, the resistance to paclitaxel that develops during treatment is a major obstacle to further treatments of GC. The present study reports that micro (mi) RNA-34a, a tumor suppressor in various types of cancer, may be an important regulator of chemoresistance in GC, as miRNA-34a mimics and inhibitors, enhance and inhibit the chemotherapeutic efficacy of paclitaxel, respectively. In addition, the present study identified that E2F transcription factor 5 (E2F5), a key oncogenic protein, is the direct target candidate of miRNA-34a. Previous studies have demonstrated that the inhibition of E2F5 by specific E2F5 small interfering RNA also increases the sensitivity of GC cells to paclitaxel. In conclusion, the present data suggest that miRNA-34a enhances the treatment of sensitive GC cells to paclitaxel by targeting E2F5. Therefore, the miRNA-34a/E2F5 axis appears to be a potential promising therapeutic target for overcoming the chemotherapeutic resistance of GC.