title: Genome-wide screening reveals that miR-195 targets the TNF-α/NF-κB pathway by down-regulating IκB kinase alpha and TAB3 in hepatocellular carcinoma.
abstract: Nuclear factor kappa B (NF-κB) is an important factor linking inflammation and tumorigenesis. In this study we experimentally demonstrated through a high-throughput luciferase reporter screen that NF-κB signaling can be directly targeted by nearly 29 microRNAs (miRNAs). Many of these miRNAs can directly target NF-κB signaling nodes by binding to their 3' untranslated region (UTR). miR-195, a member of the miR-15 family, is frequently down-regulated in gastrointestinal cancers, especially in hepatocellular carcinoma (HCC). The expression level of miR-195 is inversely correlated with HCC tumor size. We further show that miR-195 suppresses cancer cell proliferation and migration in vitro and reduces tumorigenicity and metastasis in vivo. Additionally, miR-195 may exert its tumor suppressive function by decreasing the expression of multiple NF-κB downstream effectors by way of the direct targeting of IKKα and TAB3.
  
  
  CONCLUSIONS
  Multiple miRNAs are involved in the NF-κB signaling pathway and miR-195 plays important inhibitory roles in cancer progression and may be a potential therapeutic target.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Shenglin
authors.initials: S
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Tian
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Zha
authors.forename: Haibing
authors.initials: H
authors.lastname: Shi
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Ge
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Linhui
authors.initials: L
authors.lastname: Liang
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C481053:TAB3 protein, human; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase