title: MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of β-catenin signaling.
abstract: Emerging evidence has linked aberrantly expressed microRNAs (miRNAs) with oncogenesis and malignant development in various human cancers. However, their specific roles and functions in gastric carcinoma (GC) remain largely undefined. In this study we identify and report a novel miRNA, miR-1225-5p, as tumor suppressor in GC development and progression. Microarray analysis revealed that there were fifty-six differentially expressed miRNAs (thirty-two upregulated and twenty-four downregulated) in GC tumor samples compared to their corresponding nontumorous tissues. Downregulation of miR-1225-5p was frequently detected in GC and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays demonstrated that ectopic overexpression of miR-1225-5p could inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth and metastasis in nude mice. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a downstream effector of miR-1225-5p which acted through β-catenin signaling pathway. These results demonstrate that miR-1225-5p serves to constrain GC growth and metastatic potential via inhibition of IRS1 and β-catenin signaling. Therefore, downregulation of miR-1225-5p is likely to be one of major molecular mechanisms accounting for the development and progression of GC.
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.|Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
authors.forename: Haiyin
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.|Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.|Department of Medicine and UC San Diego Moores Cancer Center, University of California-San Diego, La Jolla, CA, USA.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Union Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Changming
authors.initials: C
authors.lastname: Huang
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
authors.forename: Jianyin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.|Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
authors.forename: Wannan
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.|Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C586244:MIRN1225 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051176:beta Catenin
keywords: gastric cancer; insulin receptor substrate-1; microRNA; microRNA-1225-5p; β-catenin