title: miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer.
abstract: Accumulated evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse signaling pathways. However, the precise role of miRNAs in gastric cancer (GC) has not been elucidated. In this study, we describe the function and regulation network of miR-491-5p in GC. miR-491-5p is frequently downregulated in GC tissues compared with adjacent non-cancerous tissues. Forced expression of miR-491-5p significantly inhibits proliferation and colony formation, and promotes apoptosis in GC cells. Through bioinformatic analysis and luciferase assays, we confirm that miR-491-5p targets Wnt3a. Silencing Wnt3a inhibits cell proliferation and induces apoptosis. Similarly, restoration of Wnt3a counteracts the effects of miR-491-5p expression. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-491-5p is regulated by Foxi1, which binds to its promoter and activates miR-491-5p expression. In conclusion, to the best of our knowledge, our findings are the first to demonstrate that Foxi1 is a key player in the transcriptional control of miR-491-5p and that miR-491-5p acts as an anti-oncogene by targeting Wnt3a/β-catenin signaling in GC. Our study reveals that Foxi1/miR-491-5p/Wnt3a/β-catenin signaling is critical in the progression of GC. Targeting the pathway described in this study may open up new prospects to restrict the progression of GC.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Department of Thoracic Surgery, Shaanxi Provincial Tumor Hospital, Xi'an Jiaotong University, 309 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Tong
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|School of Public Health, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Guo
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.|Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C477894:FOXI1 protein, human; D051858:Forkhead Transcription Factors; C551410:MIRN491 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin