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

• Published in: Biochemical and biophysical research communications 2016-10, Vol.479 (1), p.91-96
• Main Authors: Wang, Ping, Li, Ziqiu, Liu, Haide, Zhou, Dongmei, Fu, Aiqin, Zhang, Enning
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Antineoplastic Agents - pharmacology; Binding Sites - genetics; Blotting, Western; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Chemosensitivity; Doxorubicin - pharmacology; Drug Resistance, Multiple - drug effects; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; EZH2; Gastric cancer; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs - genetics; miR-126; Mutation; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Vincristine - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.09.040

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. •Aberrant expression of miR-126 is associated with chemoresistance.•Ectopic expression of miR-126 re-sensitizes drug-resistant GC cells to chemotherapy.•EZH2 is a direct target of miR-126.•Restoration of EZH2 expression blocks the suppressive roles of miR-126.