MiR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.
Multidrug resistance (MDR) is the main obstacle to successful chemotherapy for patients with gastric cancer. The microRNA miR-218 influences various pathobiological processes in gastric cancer, and its down-regulation in this disease raises the question of whether it normally inhibits MDR. In this study we observed that two MDR gastric cancer cell lines showed lower expression of miR-218 compared with their chemosensitive parental cell line. Overexpressing miR-218 chemosensitizes gastric cancer cells, slowed efflux of adriamycin, and accelerated drug-induced apoptosis. We identified the smoothened (SMO) gene as a functional target of miR-218, and found that SMO overexpression counteracts the chemosensitizing effects of miR-218. These findings suggest that miR-218 inhibits MDR of gastric cancer cells by down-regulating SMO expression.
Department of Abdominal Surgery (Section 2), Affiliated Cancer Hospital of Guangzhou Medical University 78 Hengzhigang Road, Guangzhou, Guangdong 510095, China.
Xiang-Liang
XL
Zhang
Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University 58 Zhongshan Er Rd, Guangzhou, Guangdong 510080, China.
Hui-Juan
HJ
Shi
Department of Surgery, Brigham and Women's Hospital and Harvard Medical School and Departments of Surgery and Pathology, Massachusetts General Hospital and Harvard Medical School Boston, MA, USA.
Ji-Ping
JP
Wang
Department of Abdominal Surgery (Section 2), Affiliated Cancer Hospital of Guangzhou Medical University 78 Hengzhigang Road, Guangzhou, Guangdong 510095, China.
Hong-Sheng
HS
Tang
Department of Abdominal Surgery (Section 2), Affiliated Cancer Hospital of Guangzhou Medical University 78 Hengzhigang Road, Guangzhou, Guangdong 510095, China.
Shu-Zhong
SZ
Cui
D015153:Blotting, Western; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D000072086:Smoothened Receptor; D013274:Stomach Neoplasms / Q000235:genetics*; D014162:Transfection
D053823:Hedgehog Proteins; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor
Gastric cancer; SMO; hedgehog; hsa-miR-218; multi-drug resistance