title: IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis.
abstract: Gastric cancer (GC) is one of the frequent causes of cancer-related death in eastern Asian population. IGF2BP2 lists in the top rank up-regulated genes in GC, but its functional role is unclear.
  
  
  
  The expression of IGF2BP3 in GC cell lines and primary samples was examined by qRT-PCR and Western blot. The biological role of IGF2BP3 was revealed by a series of functional in vitro studies. Its regulation by microRNAs (miRNAs) was predicted by TargetScan and confirmed by luciferase assays and rescue experiments.
  
  
  
  IGF2BP3 ranked the No.1 of the up-regulated genes by expression microarray analysis in GC cell lines. The expression level of IGF2BP3 was observed in GC tissues comparing with non-tumorous gastric epitheliums. The up-regulated IGF2BP3 expression was associated with poor disease specific survival. IGF2BP3 knockdown significantly inhibited cell proliferation and invasion. Apart from copy number gain, IGF2BP3 has been confirmed to be negatively regulated by tumor-suppressive miRNA, namely miR-34a. The expression of miR-34a showed negative correlation with IGF2BP3 mRNA expression in primary GC samples and more importantly, re-overexpression of IGF2BP3 rescued the inhibitory effect of miR-34a.
  
  
  
  We compressively revealed the oncogenic role of IGF2BP3 in gastric tumorigenesis and confirmed its activation is partly due to the silence of miR-34a. Our findings identified useful prognostic biomarker and provided clinical translational potential.
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Sir Y.K. Pao Cancer Center, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Sir Y.K. Pao Cancer Center, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Ho Lam
authors.initials: HL
authors.lastname: Siu
authors.affiliation: Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Chi Chun
authors.initials: CC
authors.lastname: Wong
authors.affiliation: Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.affiliation: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.|School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Alfred S L
authors.initials: AS
authors.lastname: Cheng
authors.affiliation: Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. kfto@cuhk.edu.hk.|Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. kfto@cuhk.edu.hk.|Sir Y.K. Pao Cancer Center, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. kfto@cuhk.edu.hk.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China. kfto@cuhk.edu.hk.
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: To
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. weikang@cuhk.edu.hk.|Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. weikang@cuhk.edu.hk.|Sir Y.K. Pao Cancer Center, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China. weikang@cuhk.edu.hk.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China. weikang@cuhk.edu.hk.
authors.forename: Wei
authors.initials: W
authors.lastname: Kang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009857:Oncogenes; D011379:Prognosis; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: C498780:IGF2BP3 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins
keywords: Gastric cancer; IGF2BP3; miR-34a