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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >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
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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

机译：全基因组筛选显示，miR-195通过下调肝细胞癌中的IκB激酶α和TAB3靶向TNF-α/NF-κB途径

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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.
机译：核因子κB（NF-κB）是连接炎症和肿瘤发生的重要因素。在这项研究中，我们通过高通量荧光素酶报道分子筛选实验证明了NF-κB信号可以直接被近29种microRNA（miRNA）靶向。这些miRNA中的许多可以通过与3'非翻译区（UTR）结合而直接靶向NF-κB信号节点。 miR-15家族的成员miR-195在胃肠道癌中尤其是在肝细胞癌（HCC）中经常下调。 miR-195的表达水平与HCC肿瘤大小成反比。我们进一步表明，miR-195在体外抑制癌细胞的增殖和迁移，并在体内减少致瘤性和转移。另外，miR-195可能通过直接靶向IKKα和TAB3降低多个NF-κB下游效应子的表达来发挥其肿瘤抑制功能。结论：多种miRNA参与NF-κB信号通路，miR-195在癌症进展中起重要的抑制作用，可能是潜在的治疗靶点。

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