MicroRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2.
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.
Department of Oncology, Yantaishan Hospital, Yantai, Shandong 264000, PR China.
Ping
P
Wang
Department of General Surgery, The People's Hospital of Rushan City, Rushan, Shandong 264500, PR China.
Ziqiu
Z
Li
Department of Radiation Oncology, Yantaishan Hospital, Yantai, Shandong 264000, PR China.
Haide
H
Liu
Department of Oncology, Yantaishan Hospital, Yantai, Shandong 264000, PR China.
Dongmei
D
Zhou
Department of Oncology, Yantaishan Hospital, Yantai, Shandong 264000, PR China.
Aiqin
A
Fu
Department of Oncology, Yantaishan Hospital, Yantai, Shandong 264000, PR China. Electronic address: enmingzh11@163.com.
Enning
E
Zhang
D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014750:Vincristine / Q000494:pharmacology
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D014750:Vincristine; D004317:Doxorubicin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
Chemosensitivity; EZH2; Gastric cancer; miR-126