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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
Author(s) -
Ding Jie,
Huang Shenglin,
Wang Ying,
Tian Qi,
Zha Ruopeng,
Shi Haibing,
Wang Qifeng,
Ge Chao,
Chen Taoyang,
Zhao Yingjun,
Liang Linhui,
Li Jinjun,
He Xianghuo
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26378
Subject(s) - microrna , cancer research , nf κb , carcinogenesis , biology , signal transduction , nfkb1 , iκb kinase , hepatocellular carcinoma , cancer , untranslated region , three prime untranslated region , metastasis , transcription factor , gene , microbiology and biotechnology , genetics , messenger rna
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. Conclusion : 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. (H epatology 2013;58:654–666)