title: Impairment of growth of gastric carcinoma by miR-133-mediated Her-2 inhibition.
abstract: Gastric carcinoma (GC) is a leading cause of cancer-related death in China. Dysregulation of microRNAs (miRNAs) has been shown to contribute to the development of GC, whereas the role of miR-133 in GC is unknown. Here, we analyzed the levels of miR-133 in GC tissues by reverse and quantitative transcription polymerase chain reaction (RT-qPCR). We overexpressed or inhibited miR-133 in GC cells. Cell growth was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis was evaluated by fluorescence-activated cell sorting (FACS) analysis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. We detected lower miR-133 levels in GC tissues compared with normal gastric tissue. Moreover, the low miR-133 levels were correlated with low survival rate. Overexpression of miR-133 inhibited cell growth and promoted apoptosis, while depletion of miR-133 increased cell growth and suppressed apoptosis. Moreover, the 3'-untranslated region (3'UTR) of Her-2, the epidermal growth factor receptor (EGFR) that transduces cell growth signals, appeared to be targeted by miR-133. Together, these data suggest that reduced miR-133 levels in GC tissues promote GC growth, which possibly contributes to a low survival rate of GC patients. MiR-133 may target Her-2 to suppress GC cell growth.
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, China.|Qingdao Cancer Hospital, Qingdao, 266042, China.
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: Qingdao Cancer Hospital, Qingdao, 266042, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, China.|Qingdao Municipal Hospital, Qingdao, 266021, China.
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Xin
authors.affiliation: Qingdao Cancer Hospital, Qingdao, 266042, China.
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Ma
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, China. shiying_xuan@163.com.|Qingdao Municipal Hospital, Qingdao, 266021, China. shiying_xuan@163.com.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Xuan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; C548234:MIRN133 microRNA, human; C508053:ERBB2 protein, human
keywords: Apoptosis; Gastric carcinoma (GC); Growth; Her-2; MiR-133; MicroRNAs (miRNA)