title: miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1.
abstract: Sp1 plays critical roles in epithelial-mesenchymal transition (EMT) of certain cancer. However, few studies have indicated whether Sp1 is involved in the EMT of gastric cancer, and whether abnormal expression of Sp1 in gastric cancer EMT is regulated in a post-transcriptional manner, and the involvement of miRNAs in this regulation. In this study, we selected 20 cases of gastric cancers, their liver metastases and para-carcinoma tissues to examine the levels of Sp1 protein and mRNA by immunohistochemistry and fluorescent PCR, which showed that Sp1 was increased in gastric cancers and their metastases compared with adjacent tissues, but there was no difference in Sp1 mRNA between these three groups, suggesting changes in Sp1 may be attributed to inactivation of post-transcriptional regulation. We verified by a luciferase reporter system that miRNA-223 binds to 3'-UTR of Sp1 gene and inhibits its translation, in agreement with negative correlation between miRNA-223 and Sp1 protein levels in gastric cancer cells. By employing TGF-β1 to induce MGC-803, BGC-823 and SGC-7901, we successfully built cellular EMT model. Then, we overexpressed miRNA-223 in the model by using a lentiviral system, which diminished EMT indicators and suppressed proliferation and invasion ability, and induced apoptosis. Finally, we verified the specificity of the regulation pathway miRNA-223/Sp1/EMT. These findings suggest that low expression of miRNA-223 in gastric cancer cells is an important cause for EMT. miRNA-223 specifically regulates the EMT process of gastric cancer cells through its target gene Sp1. Overexpression of miRNA-223 in these cells inhibits EMT via the miRNA-223/Sp1/EMT pathway.
authors.affiliation: School of Basic Medical Science, Harbin Medical University, Harbin, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: School of Basic Medical Science, Harbin Medical University, Harbin, P.R. China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Department of Anesthesiology, The Second Tumor Hospital of Heilongjiang Province, Harbin, P.R. China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Hu
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, P.R. China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Respiratory Medicine, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, P.R. China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Han
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, P.R. China.
authors.forename: Yuezhen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, P.R. China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Feng
authors.affiliation: School of Basic Medical Science, Harbin Medical University, Harbin, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: School of Basic Medical Science, Harbin Medical University, Harbin, P.R. China.
authors.forename: Yukuan
authors.initials: Y
authors.lastname: Feng
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; C525067:MIR223, human; C108209:SP1 protein, human