MicroRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2.

Abstract Chemotherapeutic insensitivity is a significant barrier for effective treatment of gastric cancer (GC). Recently, emerging evidence has demonstrated that microRNAs (miRNAs) are critically involved in drug resistance. Here, by a large-scale screen, we noticed low expression of miR-126 in the drug-resistant GC cell lines SGC7901/VCR and SGC7901/ADR compared with their parental cell line SGC7901. Ectopic expression of miR-126 increased sensitivity of SGC7901/VCR and SGC7901/ADR cells to vincristine (VCR) and adriamycin (ADR). Mechanistically, Enhancer of Zeste Homolog 2 (EZH2) was identified as a direct target of miR-126. Genetic silencing of EZH2 mirrored the effects of miR-126 in drug resistance, and restoration of EZH2 blocked the inhibitory effect of miR-126 on GC. Taken together, our results suggest that miR-126 is a tumor suppressor by sensitizing GC cells to chemotherapy and provide a potential therapeutic approach in cancer treatment.