title: Wnt/β-catenin signaling inhibits FBXW7 expression by upregulation of microRNA-770 in hepatocellular carcinoma.
abstract: FBXW7 (F-box and WD repeat domain-containing 7) is the F-box protein component of a Skp1-Cul1-F-box protein-type (SCF-type) ubiquitin ligase. Previous studies have shown that FBXW7 serves as a tumor suppressor and is frequently downregulated in many types of human neoplasms. However, the molecular mechanisms for its downregulation remain poorly understood. Hyperactivation of Wnt/β-catenin signaling pathway is viewed as crucial for tumorigenesis, including hepatocellular carcinoma (HCC). In the present study, we show that protein levels, but not message RNA, of FBXW7 were suppressed by Wnt3a treatment or transfection of a constitutively activated β-catenin in HCC cells. Besides, microRNA-770 was identified as an important downstream target of Wnt/β-catenin signaling, to inhibit FBXW7 expression through targeting its 3'-untranslated region. Thus, our results suggest a previously unknown Wnt/β catenin-miR-770-FBXW7 molecular network in the HCC development.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), 197, Rui Jin Er Road, Shanghai, 200025, People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Jianli Second People's Hospital, Jianli, Hubei, 433325, People's Republic of China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Yang
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China. liubin3575630@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China. zhixiangwu@yahoo.com.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C000609533:MIRN-770 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases
keywords: FBXW7; Hepatocellular carcinoma (HCC); MicroRNA-770; Wnt/β catenin