title: miR-133b acts as a tumor suppressor and negatively regulates FGFR1 in gastric cancer.
abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate protein expression by binding protein-coding mRNAs and repressing translation. Accumulating evidence suggests that miRNAs are involved in cancer development and progression, acting as either tumor suppressors or oncogenes. Intriguingly, it has been shown that miR-133b was significantly downregulated in several types of cancers. However, its role and relevance in gastric cancer are still largely unknown. We showed that miR-133b was downregulated in human gastric cancer tissues and cell lines compared with nontumor counterparts by quantitative RT-PCR analysis. Overexpression of miR-133b could inhibit cell proliferation and colony formation of the gastric cancer cell lines MKN-45 and SGC-7901. Bioinformatics analysis indicated two putative miR-133b binding sites in the 3'-untranslated region of fibroblast growth factor receptor 1 (FGFR1) mRNA. In dual-luciferase reporter assay, miR-133b reduced the luciferase activity of Luc-FGFR1-wt, and mutation of miR-133b binding sites abolished the inhibitory effect of miR-133b. In this study, we found that miR-133b reduced the protein but not the mRNA levels of endogenous FGFR1. Furthermore, FGFR1 expression was upregulated in gastric cancer tissues and inversely correlated with miR-133b expression. Finally, knockdown of FGFR1 inhibited the growth of MKN-45 cells in a dose-dependent manner and overexpression of FGFR1 promoted the growth of GES-1 cells. These results indicate that miR-133b targets FGFR1 and inhibits gastric cancer cell growth, suggesting that it may serve as a tumor suppressive target in gastric cancer therapy.
authors.affiliation: Department of General Surgery, The Second Hospital of Jilin University, No.218, Zi Qiang Str, Nan Guan District, Changchun, 130041, Jilin Province, China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wen
authors.forename: Songhe
authors.initials: S
authors.lastname: Li
authors.forename: Fujian
authors.initials: F
authors.lastname: Ji
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Weidong
authors.initials: W
authors.lastname: Jiang
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhu
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005753:Gastric Mucosa / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1