title: miRNA-145 targets v-ets erythroblastosis virus E26 oncogene homolog 1 to suppress the invasion, metastasis, and angiogenesis of gastric cancer cells.
abstract: Recent evidence shows that v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) is implicated in tumor development and progression. However, the clinical potentials and underlying mechanisms of Ets1 in gastric cancer progression and metastasis remain largely unknown. In this study, Ets1 immunostaining was identified in 56 of 84 (66.7%) gastric cancer tissues, which was correlated with tumor invasion and metastasis. In gastric cancer specimens and cell lines, miRNA-145 (miR-145) was downregulated and inversely correlated with Ets1 expression. Bioinformatics analysis and luciferase reporter assay revealed that miR-145 directly targeted the 3'-untranslated region (3'-UTR) of Ets1 mRNA. Overexpression or knockdown of miR-145 responsively altered both the mRNA and protein levels of Ets1 and its downstream genes, matrix metalloproteinase (MMP-1)-1 and -9, in gastric cancer cell lines SGC-7901 and MKN-45. Ectopic expression of miR-145 suppressed the invasion, metastasis, and angiogenesis of SGC-7901 and MKN-45 cells in vitro and in vivo. In addition, the effects of miR-145 on Ets1 expression, migration, invasion, and angiogenesis were rescued by restoration of Ets1 expression in these cells. Furthermore, anti-miR-145 inhibitor promoted the migration, invasion, and angiogenesis, whereas siRNA-mediated Ets1 knockdown phenocopied the effects of miR-145 overexpression in gastric cancer cells. These results show that miR-145 suppresses Ets1 expression via the binding site in the 3'-UTR, thus inhibiting the invasion, metastasis, and angiogenesis of gastric cancer cells.
authors.affiliation: Department of Pathology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, PR China.
authors.forename: Liduan
authors.initials: L
authors.lastname: Zheng
authors.forename: Jiarui
authors.initials: J
authors.lastname: Pu
authors.forename: Teng
authors.initials: T
authors.lastname: Qi
authors.forename: Meng
authors.initials: M
authors.lastname: Qi
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Xuan
authors.initials: X
authors.lastname: Xiang
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Qiangsong
authors.initials: Q
authors.lastname: Tong
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D056970:Co-Repressor Proteins; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D018832:Molecular Chaperones; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D009687:Nuclear Proteins