title: MicroRNA-542-3p suppresses cell growth of gastric cancer cells via targeting oncogene astrocyte-elevated gene-1.
abstract: MicroRNAs (miRNAs) have been suggested to play critical roles in tumorigenesis as well as in the development of therapies for the treatment of cancers. However, the tumor-associated miRNAs in gastric cancers remain poorly understood. Here, we report on miR-542-3p in gastric cancers, which has been widely studied in other cancers as a tumor suppressor. Real-time quantitative PCR analysis demonstrated that miR-542-3p was significantly down-regulated in gastric cancer tissues (p < 0.0001) and cell lines (p < 0.001). Overexpression of miR-542-3p significantly inhibited cell growth of gastric cancer cells both in vitro (p < 0.01) and in vivo (p < 0.01). Notably, overexpression of miR-542-3p apparently reduced the protein expression of astrocyte-elevated gene-1 (AEG-1) (p < 0.01). The dual-luciferase reporter assay validated that miR-542-3p directly bound the 3'-untranslated region (UTR) of AEG-1, which could be abolished by mutation of the predicted miR-542-3p binding site. Furthermore, overexpression of miR-542-3p markedly inhibited the activation of oncogenic signaling pathways including the Akt, β-catenin and nuclear factor-κB pathways. Additionally, overexpression of AEG-1 without the 3'-UTR partially reversed the cell growth arrest induced by miR-542-3p overexpression in gastric cancer cells (p < 0.05). Taken together, these data suggest that miR-542-3p might function as a tumor suppressor in gastric cancer, potentially by targeting the oncogene AEG-1, implying a potential role for miR-542-3p in the development of therapeutic methods for gastric cancer.
authors.affiliation: Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Shen
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Si
authors.forename: Zhugong
authors.initials: Z
authors.lastname: Yang
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Yuan
authors.forename: Xiefu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; C572357:MIRN542 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins