Genome-wide screening reveals that miR-195 targets the TNF-/NF-B pathway by down-regulating IB kinase alpha and TAB3 in hepatocellular carcinoma

Nuclear factor kappa B (NF-B) is an important factor linking inflammation and tumorigenesis. In this study we experimentally demonstrated through a high-throughput luciferase reporter screen that NF-B signaling can be directly targeted by nearly 29 microRNAs (miRNAs). Many of these miRNAs can directly target NF-B 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-B downstream effectors by way of the direct targeting of IKK and TAB3. Conclusion: Multiple miRNAs are involved in the NF-B signaling pathway and miR-195 plays important inhibitory roles in cancer progression and may be a potential therapeutic target. (Hepatology 2013;58:654-666)